Cardiovascular Implications and Therapeutic Considerations in COVID-19 Infection.

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has profoundly impacted all fields of medicine. Infection with SARS-CoV-2 and the resulting coronavirus of 2019 (COVID-19) syndrome has multiorgan effects. The pandemic has united researchers from bench to bedside in attempts to understand the pathophysiology of the disease and define optimal treatment strategies. Cardiovascular disease is highly prevalent and a leading cause of death across gender, race, and ethnic groups. As the pandemic spreads, there is increasing concern about the cardiovascular effects of the viral infection and the interaction of infection with existing cardiovascular disease. Additionally, there are concerns about the cardiac effects of the numerous treatment agents under study. It will be essential for cardiologists to understand the interplay between underlying cardiac comorbidities, acute cardiovascular effects of COVID-19 disease, and adverse effects of new treatments. Here we describe emerging evidence of the epidemiology of SARS-CoV-2 infection and underlying cardiovascular disease, the evidence for direct myocardial injury in SARS-CoV-2 infection, the specific presentations of cardiovascular involvement by SARS-CoV-2, and the cardiac effects of emerging treatments.

Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart Disease.

BACKGROUND: Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared with isolated postcapillary. However, it remains unclear whether increased mortality in combined post- and precapillary pulmonary hypertension is simply a result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) is a measure of total right ventricular afterload, reflecting both resistive and pulsatile components. We aimed to test whether pulmonary Ea discriminates survivors from nonsurvivors in patients with pulmonary hypertension due to left heart disease and if it does so better than other hemodynamic parameters associated with combined post- and precapillary pulmonary hypertension. METHODS AND RESULTS: We combined 3 large heart failure patient cohorts (n=1036) from academic hospitals, including patients with pulmonary hypertension due to heart failure with preserved ejection fraction (n=232), reduced ejection fraction (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models, pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance and the transpulmonary gradient. Along with pulmonary arterial compliance, pulmonary Ea remained predictive of survival in patients with normal pulmonary vascular resistance. The diastolic pulmonary gradient did not predict mortality. In addition, in a subset of patients with echocardiographic data, Ea and pulmonary arterial compliance were better discriminators of right ventricular dysfunction than the other parameters. CONCLUSIONS: Pulmonary Ea and pulmonary arterial compliance more consistently predicted mortality than pulmonary vascular resistance or transpulmonary gradient across a spectrum of left heart disease with pulmonary hypertension, including patients with heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and pulmonary hypertension with a normal pulmonary vascular resistance.

Poor survival in patients with scleroderma and pulmonary hypertension due to heart failure with preserved ejection fraction.

Pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF) has been poorly studied in patients with systemic sclerosis (SSc). We sought to compare clinical characteristics and survival of SSc patients with PH-HFpEF (SSc-PH-HFpEF) versus pulmonary arterial hypertension (SSc-PAH). We hypothesized that patients with SSc-PH-HFpEF have a similar poor overall prognosis compared with patients with SSc-PAH when matched for total right ventricular load. The analysis included 117 patients with SSc-PH (93 with SSc-PAH versus 24 with SSc-PH-HFpEF) enrolled prospectively in the Johns Hopkins PH Registry. We examined baseline demographics and hemodynamics at diagnostic right heart catheterization (RHC), two-dimensional echocardiographic characteristics, six-minute walking distance (6MWD), treatment modalities, and laboratory values (serum NT-proBNP, creatinine, uric acid, and sodium), and assessed survival. Demographics and clinical features were similar between the two groups. Baseline RHC showed significantly higher pulmonary and right heart pressures in the SSc-PH-HFpEF compared with the SSc-PAH group. Trans-pulmonary gradient (TPG), however, was equally elevated without significant difference between the groups. SSc-PH-HFpEF patients had left atrial enlargement on echocardiography compared with SSc-PAH patients. No significant differences were found between groups for 6MWD, NT-proBNP, and other laboratory values. Although overall median survival time was 4.6 years with no difference in mortality rate between the two groups (SSc-PH-HFpEF versus SSc-PAH: 75% versus 59%; P = 0.26), patients with SSc-PH-HFpEF had a twofold increased risk of death compared with SSc-PAH patients after adjusting for hemodynamics. Concomitant intrinsic pulmonary vascular disease and HFpEF likely contribute to very poor survival in patients with SSc-PH-HFpEF.

Right ventricular remodeling in idiopathic and scleroderma-associated pulmonary arterial hypertension: two distinct phenotypes.

Patients with scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) have worse survival than patients with idiopathic PAH (IPAH). We hypothesized that the right ventricle (RV) adapts differently in SSc-PAH versus IPAH. We used cardiac magnetic resonance imaging (cMRI) and hemodynamic characteristics to assess the relationship between RV morphology and RV load in patients with SSc-PAH and IPAH. In 53 patients with PAH (35 with SSc-PAH and 18 with IPAH) diagnosed by right heart catheterization (RHC), we examined cMRIs obtained within 48 hours of RHC and compared RV morphology between groups. Regression analysis was used to assess the association between diagnosis (IPAH vs. SSc-PAH) and RV measurements after adjusting for age, sex, race, body mass index (BMI), left ventricular (LV) mass, and RV load. There were no significant differences in unadjusted comparisons of cMRI measurements between the two groups. Univariable regression showed RV mass index (RVMI) was linearly associated with measures of RV load in both the overall cohort and within each group. Multivariable linear regression models revealed a significant interaction between disease type and RVMI adjusting for pulmonary vascular resistance (PVR), age, sex, race, BMI, and LV mass. This model showed a decreased slope in the relationship between RVMI and PVR in the SSc-PAH group compared with the IPAH group. RVMI varies linearly with measures of RV load. After adjusting for multiple potential confounders, patients with SSc-PAH demonstrated significantly less RV hypertrophy with increasing PVR than patients with IPAH. This difference in adaptive hypertrophy may in part explain previously observed decreased contractility and poorer survival in SSc-PAH.

Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension.

BACKGROUND: Systemic sclerosis­associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis­related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function. METHODS AND RESULTS: We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis­related pulmonary hypertension with interstitial lung disease, and 67 IPAH). An inverse relation between pulmonary resistance and compliance was similar for all 3 groups, with a near constant resistance×compliance product. RV pressure­volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7), as well as SSc without PH (n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of RV load (arterial elastance [Ea]), and RV pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (pulmonary vascular resistance=7.0±4.5 versus 7.9±4.3 Wood units; Ea=0.9±0.4 versus 1.2±0.5 mm Hg/mL; pulmonary arterial compliance=2.4±1.5 versus 1.7±1.1 mL/mm Hg; P>0.3 for each). Although SScPAH did not have greater vascular stiffening compared with IPAH, RV contractility was more depressed (Ees=0.8±0.3 versus 2.3±1.1, P<0.01; Msw=21±11 versus 45±16, P=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 versus 2.1±1.0; P=0.03). This ratio was higher in SSc without PH (Ees/Ea=2.3±1.2; P=0.02 versus SScPAH). CONCLUSIONS: RV dysfunction is worse in SScPAH compared with IPAH at similar afterload, and may be because of intrinsic systolic function rather than enhanced pulmonary vascular resistive and pulsatile loading.

The nature and prevalence of disability in a Ghanaian community as measured by the Language Independent Functional Evaluation.

INTRODUCTION: The current study uses the Language Independent Functional Evaluation (L.I.F.E.) to evaluate disability in a smaller Ghanaian coastal town to characterize the extent and nature of disability. The L.I.F.E. is a video animated, language free equivalent of the standard 10-item verbal/written Barthel Index functional assessment. METHODS: Over a four-month period, the L.I.F.E. survey was given to members of the village of Anomabo in a preliminary survey which consisted of recruitment in an un-controlled manner, followed by a systematic, comprehensive survey of three neighborhood clusters. Basic demographics were also collected, along with the observer's assessment of disability. RESULTS: 541 inhabitants (264 in the preliminary survey and 277 in systematic survey) completed the L.I.F.E. Participants ranged from 7-100 years old (mean age 32.88, s.d. 20.64) and were 55.9% female. In the systematic study, 16.6% of participants had a less than perfect score on the L.I.F.E., indicating some degree of impairment. Significant differences were found between age groups, but not between sexes, the preliminary and systematic survey, and study location (a=.05). CONCLUSION: The L.I.F.E. and this study methodology can be used to measure the prevalence of disability in African communities. Disability in this community was higher than the frequently cited estimate of 10%. African policymakers can use the L.I.F.E. to measure disability and thus more rationally allocate resources for medical rehabilitation.

The ligamentum flavum at L4-5: relationship with anthropomorphic factors and clinical findings in older persons with and without spinal disorders.

OBJECTIVE: To examine the relationship between ligamentum flavum thickness and clinical spinal stenosis. DESIGN: A validation study. SETTING: Clinical research laboratory. PATIENTS: A total of 119 subjects from the Michigan Spinal Stenosis Study (MSSS). METHODS: Two new measurement techniques were compared by use of magnetic resonance images of 4 asymptomatic subjects by 2 examiners. The technique with the best interrater reliability was then used to measure the ligamentum flavum at L4-L5 in 119 subjects in the MSSS who, on the basis of clinical examination without imaging, were thought to have lumbar stenosis, mechanical back pain, or no pain. These findings were related to other radiologic findings, demographics, clinical severity, and electrodiagnostic findings. MAIN OUTCOME MEASUREMENTS: Perpendicular on the inside of the spinal canal from the deepest point of concavity of the lamina to the edge of the ligament. RESULTS: The ligamentum flavum width measurement had high interrater (r = 0.774) and intrarater (r = 0.768) reliability. In 28 asymptomatic volunteers, ligamentum flavum width averaged 5.72 ± 0.95 mm, with the left side significantly thinner than the right (t = 2.117, P = .044), and thicker ligaments with age (r = 0.653, P < .001). Asymptomatic persons whom radiologists thought had stenosis had thicker ligaments (t = 2.273, P = .032). Persons with clinical stenosis (n = 48) and mechanical pain (n = 43) had ligament thickness similar to that of asymptomatic volunteers. Among patients with clinical stenosis, ligamentum flavum thickness did not relate to symptom severity (pedometer and laboratory ambulation tests, Pain Disability Index, and visual analog scale for pain). Most neurophysiological findings had no relationship with ligamentum flavum width, except the presence of limb fibrillation potentials related to a thinner ligament (t = 2.915, P = .004). CONCLUSIONS: The measurement technique is standardized for the ligamentum flavum for future use. Although the ligamentum flavum appears to get thicker with age, other factors, including clinical diagnosis, pain, and function, do not appear to relate to the ligamentum flavum width.