To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFβ signaling, and ADAMTS13, the von Willebrand Factor–cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.
Introduction: The classification and management of pulmonary hypertension (PH) is challenging due to clinical and hemodynamic heterogeneity of patients. We sought to identify distinct phenogroups of PH that are at particularly high-risk for adverse events. Methods: A hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH (mean pulmonary artery pressure > 20 mmHg at rest) were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant or valvular surgery. K-prototypes, an unsupervised clustering algorithm, was used to cluster patients into subgroups based on 11 clinical covariates. The optimal number of clusters was determined using the silhouette method. Results: Among 5208 patients with mean age 64 (SD 12) years, 39% women, we identified 6 phenogroups when clustering on baseline clinical comorbidities ( Table 1 ). Phenogroups 2 and 4 had the greatest baseline prevalence of heart failure (both) and diabetes (group 4). Over a median follow-up of 6.3 (IQR 3.6 to 9.8) years we observed 2182 deaths and 2002 major cardiovascular events (MACE). Phenogroups 2 and 4 had the highest risk for future adverse events including death (age and sex adjusted HR 1.33, 95% CI 1.05-1.68 and 1.42, 95% CI 1.13-1.77, each compared with the lowest risk group 3 respectively) and MACE (HR 5.97, 95% CI 4.83-7.38 and 4.06, 95% CI 3.30-4.99, compared with group 3 respectively; Figure 1 ). Conclusions: Cluster-based analyses identify patients with PH and specific comorbid cardiovascular burden that are at higher risk for adverse clinical outcomes. Further studies are needed to better understand clinical heterogeneity among patients with PH.
ABSTRACT Background Subspecialty consultation in inpatient care is increasing. Teaching by subspecialty fellows in a consultation setting may be an important source of work-based learning for students and residents. However, teaching and evaluation of learners in this context may be challenging due to personal and systems-based barriers. Objective We developed and evaluated a framework designed to overcome barriers to teaching and to improve fellow teaching skills during inpatient consultation. Methods The PARTNER (Partner with resident, Assess the learner, Reinforce positives, Teaching objectives, New knowledge, Execute recommendations, Review) framework was delivered to rheumatology and pulmonary and critical care medicine fellows at 3 academic medical centers as part of a 2-session Fellow as Clinical Teacher (FACT) curriculum. Fellows' teaching skills were evaluated using an objective structured teaching exercise (OSTE) pre- and postcurriculum, and at the end of the academic year. Self-assessment surveys were used to evaluate fellows' self-perception of teaching skills. Results Twelve of 16 eligible fellows (75%) participated in the program and completed 73 OSTE cases. Teaching skills measured by OSTEs and self-assessment surveys improved after administration of the FACT curriculum. There was no significant skill decay at the end-of-year evaluation. The curriculum was rated highly, and 73% (8 of 11) of fellows stated they would teach more frequently as a result of the intervention. Conclusions The FACT curriculum was practical and feasible, and significantly improved fellows' teaching skills teaching during inpatient consultation.
Background Cardiorespiratory fitness is not limited by pulmonary mechanical reasons in the majority of adults. However, the degree to which lung function contributes to exercise response patterns among ostensibly healthy individuals remains unclear. Methods We examined 2314 Framingham Heart Study participants who underwent cardiopulmonary exercise testing (CPET) and pulmonary function testing. We investigated the association of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC and diffusing capacity of the lung for carbon monoxide ( D LCO ) with the primary outcome of peak oxygen uptake ( V ′ O 2 ) along with other CPET parameters using multivariable linear regression. Finally, we investigated the association of total and peripheral pulmonary blood vessel volume with peak V ′ O 2 . Results We found lower FEV 1 , FVC and D LCO were associated with lower peak V ′ O 2 . For example, a 1 L lower FEV 1 and FVC was associated with a 7.1% (95% CI 5.1–9.1%) and 6.0% (95% CI 4.3–7.7%) lower peak V ′ O 2 , respectively. By contrast, FEV 1 /FVC was not associated with peak V ′ O 2 . Lower lung function was associated with lower oxygen uptake efficiency slope, oxygen pulse slope, V ′ O 2 at anaerobic threshold (AT), minute ventilation ( V ′ E ) at AT and breathing reserve. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V ′ O 2 . Conclusions In a large, community-based cohort of adults, we found lower FEV 1 , FVC and D LCO were associated with lower exercise capacity, as well as oxygen uptake efficiency slope and ventilatory efficiency. In addition, lower total and peripheral pulmonary blood vessel volume were associated with lower peak V ′ O 2 . These findings underscore the importance of lung function and blood vessel volume as contributors to overall exercise capacity.
Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF<50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI <450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p<0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p<0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p<0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.
