Since the first SARS-CoV-2 infections were identified in December 2019, the COVID-19 pandemic has significantly increased morbidity and mortality around the world.¹ Previous epidemics of viruses from the coronavirus family, such as SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), have developed into persistent symptoms in infected individuals, including severe fatigue, decreased quality of life (QOL), and shortness of breath, as well as behavioral and psychological problems.¹ These persistent postviral symptoms have been associated with a substantial burden to health care systems.

Objective: Primary Sjögren's syndrome (SS) may lead to lymphoproliferative disease (LPD) and death in certain patients. We sought to determine the incidence and predictors of adverse long‐term outcomes to achieve a rational predictive classification of the syndrome.Methods: Predictive modeling was performed in a cohort of 723 consecutive patients with primary SS (587 newly diagnosed [incident] cases and 136 prevalent cases).Results: During 4,384 person‐years of followup, we recorded 39 deaths (7 due to lymphoma) and 38 diagnoses of LPD. The standardized mortality ratio was 1.15 (95% confidence interval [95% CI] 0.86–1.73) compared with the general population of Greece. In incident cases, the probability of LPD was 2.6% at 5 years and 3.9% at 10 years. Mortality rates were significantly higher in patients with low C4 levels at the first study visit (hazard ratio [HR] 4.39, 95% CI 2.18–8.83). LPD was independently predicted by the presence of parotid enlargement (HR 5.21, 95% CI 1.76–15.4), palpable purpura (HR 4.16, 95% CI 1.65–10.5), and low C4 levels (HR 2.40, 95% CI 0.99–5.83) at the first study visit. All patients who eventually developed lymphoma resulting in death during the followup period had either low C4 levels or palpable purpura at the first study visit. Training‐validation split‐cohort modeling confirmed the predictive importance of low C4 levels and palpable purpura, both of which were present in 20.9% of patients at their first visit.Conclusions: In patients with primary SS, 1 in 5 deaths is attributable to lymphoma. The presence of palpable purpura and low C4 levels at the first visit adequately distinguishes high‐risk patients (type I primary SS) from patients with an uncomplicated disease course (type II [low‐risk] primary SS).

Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) 35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. Methods: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. Results: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9–21.8; P <0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8–13.5; P =0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6–266.6; P <0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9–22.3; P <0.0001), SCD (HR, 4.8; 95% CI, 1.7–13.8; P =0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8–271.4; P 5% compared with those without LGE were 10.6 (95% CI, 3.9–29.4), 4.9 (95% CI, 1.3–18.9), and 11.8 (95% CI, 4.3–32.3), respectively. Conclusions: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. Clinical Trial Registration: URL: http://clinicaltrials.gov . Unique identifier: NCT00930735.

This study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort. The relationship between LGE and prognosis in DCM is incompletely understood. The authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM. Of 874 patients (588 men, median age 52 years) followed for a median of 4.9 years, 300 (34.3%) had nonischemic LGE. Estimated adjusted hazard ratios for patients with an LGE extent of 0 to 2.55%, 2.55% to 5.10%, and >5.10%, respectively, were 1.59 (95% confidence interval [CI]: 0.99 to 2.55), 1.56 (95% CI: 0.96 to 2.54), and 2.31 (95% CI: 1.50 to 3.55) for all-cause mortality, and 2.79 (95% CI: 1.42 to 5.49), 3.86 (95% CI: 2.09 to 7.13), and 4.87 (95% CI: 2.78 to 8.53) for the SCD endpoint. There was a marked nonlinear relationship between LGE extent and outcome such that even small amounts of LGE predicted a substantial increase in risk. The presence of septal LGE was associated with increased mortality, but SCD was most associated with the combined presence of septal and free-wall LGE. Predictive models using LGE presence and location were superior to models based on LGE extent or pattern. In DCM, the presence of septal LGE is associated with a large increase in the risk of death and SCD events, even when the extent is small. SCD risk is greatest with concomitant septal and free-wall LGE. The incremental value of LGE extent beyond small amounts and LGE pattern is limited.

Background: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. Methods: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. Results: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm ² /m ² ; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11–2.04; P =0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03–1.22; P =0.007), and scar presence (HR, 2.39; 95% CI, 1.40–4.05; P =0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P <0.001) and cardiovascular (15.0% versus 4.8%; P <0.001) mortality, regardless of intervention (transcatheter AVR, P =0.002; surgical AVR, P =0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05–1.17; P <0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01–1.17; P <0.001). Conclusions: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Background: Aortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR). Methods: Asymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified. RESULTS: In 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8–4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%–158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%–25%) reduction in left ventricular mass index ( P <0.0001) and an 11% (4%–16%) reduction in indexed extracellular volume ( P =0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6–8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1–8.0 g]; P =0.23), with no evidence of regression even out to 2 years. Conclusions: In patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01755936 and NCT01679431.