Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity.

BACKGROUND: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood. OBJECTIVES: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression. METHODS: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygAC). CVD events were ascertained from electronic health records. RESULTS: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygAC (standardized ß: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygAC reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023). CONCLUSIONS: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression.

Clinical Biochemistry of Serum Troponin.

Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement.

Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk.

BACKGROUND: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (ACl/m) has been linked to lower MACE risk, but the mechanisms are unclear. OBJECTIVES: The purpose of this study was to evaluate whether the association between ACl/m and MACE is mediated by decreased SNA. METHODS: Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (<1, 1-14, or >14 drinks/week, respectively). RESULTS: Of 53,064 participants (median age 60 years, 60% women), 23,920 had no/minimal alcohol consumption and 27,053 ACl/m. Over a median follow-up of 3.4 years, 1,914 experienced MACE. ACl/m (vs none/minimal) associated with lower MACE risk (HR: 0.786; 95% CI: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, ACl/m (vs none/minimal) associated with decreased SNA (standardized beta -0.192; 95% CI: -0.338 to -0.046; P = 0.01). Lower SNA partially mediated the beneficial effect of ACl/m on MACE (log OR: -0.040; 95% CI: -0.097 to -0.003; P < 0.05). Further, ACl/m associated with larger decreases in MACE risk among individuals with (vs without) prior anxiety (HR: 0.60 [95% CI: 0.50-0.72] vs 0.78 [95% CI: 0.73-0.80]; P interaction = 0.003). CONCLUSIONS: ACl/m associates with reduced MACE risk, in part, by lowering activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol's potential health detriments, new interventions with similar effects on SNA are needed.

Focused cardiac ultrasound in pregnancy.

Cardiac disease in pregnancy is an important cause of maternal morbidity and mortality. In many high-income countries, acquired cardiac disease is now the largest cause of maternal mortality. Given its prevalence in low- and middle-income countries (LMICs), rheumatic heart disease is the most common cause of cardiac disease in pregnancy worldwide and is associated with poor maternal outcome. The diagnosis of cardiac disease in pregnancy is often delayed resulting in excess maternal morbidity and mortality. Maternal mortality review committees have suggested that prompt recognition and treatment of heart disease in pregnancy may improve maternal outcome. Given the similarities between symptoms of normal pregnancy and those of cardiac disease, the clinical diagnosis of heart disease in pregnancy is challenging with echocardiography being the primary diagnostic modality. Focused cardiac ultrasound (FOCUS) at the point of care provides supplemental data to the history and physical examination and has been demonstrated to permit early diagnosis and improvement in the management of cardiac disease in emergency medicine, intensive care, and anesthesia. It has also been demonstrated to be useful in surveillance for rheumatic heart disease in LMICs. The use of FOCUS may allow earlier and more accurate diagnosis of cardiac disease in pregnancy with the potential to decrease morbidity and mortality in both developed and developing countries.

The combined effect of air and transportation noise pollution on atherosclerotic inflammation and risk of cardiovascular disease events.

BACKGROUND: Air pollution and noise exposures individually associate with major adverse cardiovascular events (MACE) via a mechanism involving arterial inflammation (ArtI); however, their combined impact on ArtI and MACE remains unknown. We tested whether dual (vs. one or neither) exposure associates with greater ArtI and MACE risk and whether MACE risk is mediated via ArtI. METHODS: Individuals (N = 474) without active cancer or known cardiovascular disease with clinical 18F-FDG-PET/CT imaging were followed for 5 years for MACE. ArtI was measured. Average air pollution (particulate matter ≤ 2.5 µm, PM2.5) and transportation noise exposure were determined at individual residences. Higher exposures were defined as noise > 55 dBA (World Health Organization cutoff) and PM2.5 ≥ sample median. RESULTS: At baseline, 46%, 46%, and 8% were exposed to high levels of neither, one, or both pollutants; 39 experienced MACE over a median 4.1 years. Exposure to an increasing number of pollutants associated with higher ArtI (standardized ß [95% CI: .195 [.052, .339], P = .008) and MACE (HR [95% CI]: 2.897 [1.818-4.615], P < .001). In path analysis, ArtI partially mediated the relationship between pollutant exposures and MACE (P < .05). CONCLUSION: Air pollution and transportation noise exposures contribute incrementally to ArtI and MACE. The mechanism linking dual exposure to MACE involves ArtI.

Racial differences in cardiopulmonary outcomes of hospitalized COVID-19 patients with acute kidney injury.

In-hospital acute kidney injury (IH-AKI) has been reported in a significant proportion of patients with COVID-19 and is associated with increased disease burden and poor outcomes. However, the mechanisms of injury are not fully understood. We sought to determine the significance of race on cardiopulmonary outcomes and in-hospital mortality of hospitalized COVID-19 patients with AKI. We conducted a retrospective cohort study of consecutive patients hospitalized in Grady Health System in Atlanta, Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. We evaluated the primary composite outcome of in-hospital cardiac events, and mortality in blacks with AKI versus non-blacks with AKI. In a subgroup analysis, we evaluated the impact of AKI in all blacks and in all non-blacks. Of 293 patients, effective sample size was 267 after all exclusion criteria were applied. The mean age was 61.4 ± 16.7, 39% were female, and 75 (28.1%) had IH-AKI. In multivariable analyses, blacks with IH-AKI were not more likely to have in-hospital cardiac events (aOR 0.3, 95% Confidence interval (CI) 0.04-1.86, p = 0.18), require ICU stay (aOR 0.80, 95% CI 0.20-3.25, p = 0.75), acute respiratory distress syndrome (aOR 0.77, 95% CI 0.16-3.65, p = 0.74), require mechanical ventilation (aOR 0.51, 95% CI 0.12-2.10, p = 0.35), and in-hospital mortality (aOR 1.40, 95% CI 0.26-7.50, p = 0.70) when compared to non-blacks with IH-AKI. Regardless of race, the presence of AKI was associated with worse outcomes. Black race is not associated with higher risk of in-hospital cardiac events and mortality in hospitalized COVID-19 patients who develop AKI. However, blacks with IH-AKI are more likely to have ARDS or die from any cause when compared to blacks without IH-AKI.

Acute on chronic severe aortic insufficiency due to rheumatoid arthritis-associated valvulitis.

Rheumatoid Arthritis associated valvular heart disease (RA-VHD) may occur in patients in varying degrees of severity. Aortic valve involvement leading to severe symptomatic aortic insufficiency is a rare complication of rheumatoid arthritis. This entity has not been well characterized and its clinical predictors are undefined. The pathology of RA-VHD can extend from benign nodular development to acute valvulitis with late-stage leaflet fibrosis and severe valvular regurgitation. In this report, we describe a rare case of acute heart failure (AHF) resulting from severe aortic valve destruction and insufficiency due to persistent chronic inflammation in a patient with long-standing RA. Persistent systemic inflammation of RA involved the aortic valve causing nodular thickening and leaflet destruction. Our patient had compensated chronic heart failure due to progressive aortic insufficiency resulting from gradual leaflet destruction. However, she suddenly developed AHF requiring valve replacement. Her clinical presentation, gross and histological images suggest an acute/subacute disruption of the friable aortic leaflets that resulted in AHF.

Left main stenting with stent dislodgement and entrapment in the common femoral artery: a successful transcatheter stent retrieval.

Proximal left main stenting in symptomatic patients with flow-limiting stenosis is an alternative revascularization strategy in individuals with low syntax score and high operative risk. Stent dislodgement is associated with adverse cardiovascular events and retrieval of fully deployed stents is generally prohibited as it increases the risk of severe complications. Stent dislodgement and entrapment in the femoral vascular system occur infrequently during percutaneous coronary interventions. In this report, we illustrate a prompt and safe transcatheter technique to successfully retrieve an expanded and dislodged coronary stent entrapped in the common femoral artery without need for a more invasive surgical approach.

Pre-existing cardiovascular disease, acute kidney injury, and cardiovascular outcomes in hospitalized blacks with COVID-19 infection.

BACKGROUND: The Corona Virus 19 (COVID-19) infection is associated with worse outcomes in blacks, although the mechanisms are unclear. We sought to determine the significance of black race, pre-existing cardiovascular disease (pCVD), and acute kidney injury (AKI) on cardiopulmonary outcomes and in-hospital mortality of COVID-19 patients. METHODS: We conducted a retrospective cohort study of blacks with/without pCVD and with/without in-hospital AKI, hospitalized within Grady Memorial Hospital in Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. The primary outcome was a composite of in-hospital cardiac events. RESULTS: Of the 293 patients hospitalized with COVID-19 in this study, 71 were excluded from the primary analysis (for race/ethnicity other than black non-Hispanic). Of the 222 hospitalized COVID-19 patients included in our analyses, 41.4% were female, 78.8% had pCVD, and 30.6% developed AKI during the admission. In multivariable analyses, pCVD (OR 4.7, 95% CI 1.5-14.8, P=0.008) and AKI (OR 2.7, 95% CI 1.3-5.5, P=0.006) were associated with increased odds of in-hospital cardiac events. AKI was associated with increased odds of in-hospital mortality (OR 8.9, 95% CI 3.3-23.9, P<0.0001). The presence of AKI was associated with increased odds of ICU stay, mechanical ventilation, and acute respiratory distress syndrome (ARDS). CONCLUSION: pCVD and AKI were associated with higher risk of in-hospital cardiac events, and AKI was associated with a higher risk of in-hospital mortality in blacks.

Efficacy and safety of chloroquine and hydroxychloroquine for treatment of COVID-19 patients-a systematic review and meta-analysis of randomized controlled trials.

The coronavirus disease 19 (COVID-19) pandemic has caused significant morbidity and mortality worldwide and an effective treatment is needed. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro antiviral activity against SARS-CoV-2 which causes the disease, but the evidence from in vivo studies so far has been inconclusive. OBJECTIVE: To evaluate the efficacy and safety of CQ and HCQ in the treatment of COVID-19. DATA SOURCES: We systematically searched the PubMed, Embase, MEDLINE, Cochrane CENTRAL, CINAHL, Scopus, Joanna Briggs Institute Database, ClinicalTrials.gov, and Chinese Clinical Trial Registry (ChiCTR) for all articles published between 01 January 2020 to 15 September 2020 on CQ/HCQ and COVID-19 using a predefined search protocol; without any language restrictions. A search of grey literature repositories (New York Academy of Medicine Grey Literature and Open Grey), and pre-publication server deposits (medRxIV and bioRxIV) was also performed. STUDY SELECTION: Randomized clinical trials (RCT) which compared CQ/HCQ to standard supportive therapy in treating COVID-19 were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted from original publications by four independent reviewers. Risk of bias was assessed using the Cochrane Collaboration's assessment tool. Data were meta-analyzed using a random-effect models. Results are reported according to PRISMA guidelines. Main Outcome(s) and Measure(s): The primary prespecified efficacy outcome was all-cause mortality. The primary safety outcome was any adverse effect attributed to use of CQ/HCQ. RESULTS: Eight RCTs were included and pooled in the mortality meta-analysis (6,592 unique participants; mean age = 59.4 years; 42% women). CQ/HCQ did not show any mortality benefit when compared to standard supportive therapy (Pooled Relative Risk [RR] 1.07; 95% CI = 0.97-1.18; I2 statistic = 0.00%). Sensitivity and sub-group analyses showed similar findings. Any adverse event was significantly higher in patients randomized to CQ/HCQ (RR = 2.51; 95% CI = 1.53-4.12; n = 1,818 patients), but the risk of developing severe adverse event was not statistically significant (RR = 0.99, 95% CI = 0.53-1.86; n = 6,456 patients). CONCLUSIONS AND RELEVANCE: Evidence from currently published RCTs do not demonstrate any added benefit for the use of CQ or HCQ in the treatment of COVID-19 patients.

Social determinants and cardiovascular care: A focus on vulnerable populations and the Jamaica experience.

The concept of social determinants of health (SDOH) describes the complex interplay of social, economic, cultural, and environmental forces that influence health and illness and result in health inequities in society. In cardiovascular disease (CVD), SDOH play a significant role in contributing to the severe morbidity and mortality that various cardiovascular diseases inflict on our societies. The components of SDOH include wealth/income, employment status, education, social interactions/support, access to medical care (including mental health services), housing, transportation, physical environment (including availability of green space, water/sanitation, air pollution, noise pollution), work environment, access to good nutrition, social and community networks, access to technology and data, exposure to crime/social disorder/violence, exposure to adverse law enforcement/bad governance, and cultural norms. Leveraging reliable SDOH data is critical to addressing healthcare needs of the community. At-risk populations must be connected to the appropriate resources needed to overcome these barriers to access to achieve better health outcomes. This review explores this theme with a focus on several vulnerable populations and offers possible strategies to reduce these inequalities. The Heart Institute of the Caribbean (HIC) was founded in 2005 to improve access to quality medical and cardiovascular services, made available to everyone regardless of their socioeconomic status. HIC has encountered and learned to navigate a myriad structural, institutional, socio-economic, cultural, and behavioral barriers to appropriate CVD care for vulnerable populations in Jamaica and the wider Caribbean. The successes attained and the lessons learned by HIC can be replicated in other nations to address social determinants that impede cardiovascular and medical care in vulnerable populations and may alleviate the access gap in high-quality care in developing countries and in underserved and marginalized communities in developed countries.

Transvenous Retrieval of a Pulmonary Artery Catheter Knot Around Pacing Leads: A Case Report.

BACKGROUND: Pulmonary Artery Catheter (PAC) knotting is a rare complication of PAC insertion. In patients with dilated right heart chambers, blind insertion of PAC significantly increases the risk of catheter knotting. We demonstrate a safe and successful approach to resolving a PAC knot around pacing leads of a cardiac resynchronization device. CASE PRESENTATION: A 63-year-old African American male with dilated cardiomyopathy and a cardiac resynchronization therapy (CRT) device for severe left ventricular systolic dysfunction required PAC insertion for hemodynamic management of acute heart failure. PAC insertion was complicated by catheter knotting around the pacing leads. The PAC was successfully retrieved using a transvenous technique. CONCLUSION: Fluoroscopy-guided insertion of PAC is advisable and preferred over blind insertion in patients with high risk of PAC entanglement. LEARNING OBJECTIVE: To highlight a potential complication of blind pulmonary artery catheter insertion and provide a safe technique to resolve catheter knots.

Anticoagulation-related nephropathy for the internist: a concise review.

Anticoagulation-related nephropathy (ARN) is a clinical entity that has significant morbidity and mortality consequences/burden but has not been well described. Consequently, ARN has been underdiagnosed and sub-optimally managed. ARN has been reported with warfarin use especially in the setting of supratherapeutic international normalized ratio (INR) but the association is far less established with the use of direct-acting oral anticoagulants (DOAC). Accelerated progression to CKD and ultimately ESRD has been reported in patients with ARN. With the expanding indications for DOAC use, there is growing concern about ARN in the setting of DOAC use and its attendant clinical and socioeconomic burden. In this review, we highlight precautionary measures to aid prompt diagnosis of ARN and suggest possible therapeutic strategies.

Sub-Saharan Africa Tackles COVID-19: Challenges and Opportunities.

As of May 2020, the global COVID-19 pandemic had reached 187 countries with more than 3.7 million confirmed cases and 263,000 deaths. While sub-Saharan Africa (SSA) has not been spared, the extent of disease is currently far less than in Europe or North America leading some to posit that climatic, genetic or other conditions will self-limit disease in this location. Nonetheless, infections in tropical Africa continue to rise at an alarming pace with the potential to soon exceed health resource availability and to exhaust a health care workforce that is already grossly under supported and ill-equipped. This perspective outlines the context of COVID-19 disease in Africa with a focus on the distinctive challenges faced by African nations and a potential best path forward.