Inflammation as orchestrator of cardiac disease progression

Real-time monitoring of cardiac disease progression using consumer electronics can be of immense benefit and realizable with the recent progress of wearables. This paper proposes a fast-acting personalized smart health wearable solution for cardiac disease monitoring using Electrocardiography (ECG). <br>

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Cardiac Events After Radiation Therapy: Combined Analysis of Prospective Multicenter Trials for Locally Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2016.71.6142 ◽

2017 ◽

Vol 35 (13) ◽

pp. 1395-1402 ◽

Cited By ~ 112

Author(s):

Robert T. Dess ◽

Yilun Sun ◽

Martha M. Matuszak ◽

Grace Sun ◽

Payal D. Soni ◽

...

Keyword(s):

Radiation Therapy ◽

Disease Progression ◽

Cardiac Disease ◽

Cardiac Event ◽

Locally Advanced ◽

Cardiac Events ◽

Eligibility Criteria ◽

Heart Dose ◽

Grade 3 ◽

Mean Heart Dose

Purpose Radiation therapy is a critical component in the care of patients with non–small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

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ECG Beat based Cardiac Disease Progression Monitoring for Wearables

10.36227/techrxiv.13298864.v1 ◽

2020 ◽

Author(s):

Preethi Krishnan ◽

bashir morshed ◽

Viswanathan Rajagopalan

Keyword(s):

Disease Progression ◽

Real Time ◽

Cardiac Disease ◽

Recent Progress ◽

Consumer Electronics ◽

Disease Monitoring ◽

Real Time Monitoring ◽

Smart Health ◽

Fast Acting

Real-time monitoring of cardiac disease progression using consumer electronics can be of immense benefit and realizable with the recent progress of wearables. This paper proposes a fast-acting personalized smart health wearable solution for cardiac disease monitoring using Electrocardiography (ECG). <br>

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Abstract P196: The Impact of MicroRNA195 on the Lkb1/AMPK Signaling Axis and Hypertrophic Cardiomyopathy

Circulation Research ◽

10.1161/res.109.suppl_1.ap196 ◽

2011 ◽

Vol 109 (suppl_1) ◽

Author(s):

Hao Chen ◽

Laurel Mckee ◽

Gustavo Untiveros ◽

Jessica Perez ◽

John Konhilas

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Disease Progression ◽

Cardiac Disease ◽

C2c12 Cells ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Ampk Signaling ◽

Ampk Pathway ◽

Signaling Axis ◽

The Impact

Objectives: MicroRNAs (miRs) have been identified as chief post-transcriptional regulators of cardiac disease progression. In addition, a critical role of the adenosine monophosphate-activated kinase (AMPK) pathway in the development of myocardial hypertrophy has been revealed. Yet, regulation of the AMPK pathway by miRs in the heart has not been addressed. We hypothesized that components of the AMPK pathway are targeted by miRs and alter AMPK signaling in a mouse model of hypertrophic cardiomyopathy (HCM). Methods and results: Using real-time PCR, a candidate miR screen that included 22 miRs implicated in pathological cardiac disease and/or metabolic dysregulation was performed on hearts from 60-, 120-, and 240-day-old transgenic HCM male mice harboring an R403Q mutation in the myosin heavy gene. Among early (60 day) elevated miRs were miR-195 and -451. Both miR-195 and -451 have conserved target sites in the 3′ UTR of CAB39 (MO25), a central component of the MO25/STRAD/LKB1 complex that acts as an upstream kinase for AMPK and its subsequent activation. We further confirmed the elevation of miR-195 and -451 by Northern blotting. Next, we demonstrated specific expression and a similar distribution pattern of miR-195 and -451 in cardiomyocytes of R403Q HCM hearts by in situ hybridization. To determine whether the conserved sites in MO25 3′ UTR acted as functional targets, either the miR-195 or miR-451 target sequence was cloned into a luciferase expression vector. MiR-195 but not miR-451 suppressed luciferase activity compared to the missense sequence control vector in C2C12 cells. In addition, over-expression of miR195 in C2C12 cells knocked down MO25 expression levels and downstream AMPK signaling (phosphorylation of Acetyl CoA carboxylase). Finally, parallel changes were measured in 60 day R403Q HCM male hearts that included reduced MO25 expression and lowered phosphorlation of AMPK and Acetyl CoA carboxylase. Conclusion: Our findings indicate that miR-195 targets the LKB1/AMPK signaling axis and suggest a functional role for miR-195 elevation in R403Q HCM disease progression.

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