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The Vibrant Philly Biotech Scene: PCCI Meeting Announcement, BioDetego Presents Colon Cancer Diagnostic Tool

Posted in Cancer and Current Therapeutics, Cancer Informatics, Cancer Prevention: Research & Programs, Clinical Diagnostics, Diagnostics and Lab Tests, Health Economics and Outcomes Research, tagged #biotech, cancer diagnostics, cancer relapse, colon cancer, cost efficient cancer diagnosis, health outcomes, healthcare, prediction of long-term prognosis, prognostic analysis on December 2, 2015| Leave a Comment »

The Vibrant Philly Biotech Scene: PCCI Meeting Announcement, BioDetego Presents Colon Cancer Diagnostic Tool

Reporter: Stephen J. Williams, Ph.D.

PCCI invites you to attend a presentation by:

BioDetego, A cancer diagnostics development company (see meeting announcement here)

Monday, December 14, 2015, 6:30PM; at the Chesterbrook (Wayne, PA) Embassy Suites Hotel (directions below)

Sponsored by:

To register please click on www.rxpcci.com and follow directions

BioDetego is developing the next generation of cancer diagnostics – identifying people that will benefit from chemotherapy with unprecedented accuracy.

Today there are no clear treatment guidelines for many people with cancer and routinely people are undertreated (the lack of chemotherapy treatment for people at risk of disease relapse) or overtreated (the unnecessary, harmful treatment of people not at risk). The resulting human and economic burden is enormous. Those undertreated face increased mortality at a cost of >$150,000 per relapse, and those overtreated suffer the harmful effects of unnecessary chemotherapy at a cost of $25,000 per person.

Supported by compelling clinical data in multiple cancer types, BioDetego is developing VASPfore, a disruptive cancer diagnostic platform that addresses this critical gap in cancer care by accurately determining each person’s risk of relapse and need for chemotherapy. The lead product, VASPfore-CRC, is poised to change the standard of care in colorectal cancer diagnosis and treatment. The test will:

– Accurately determine individual risk of relapse and chemotherapy need

– Provide 100% actionable information to reduce harmful under- and overtreatment

– Improve health outcomes

– Deliver savings by reducing payor costs

BioDetego’s lead product VASPfore-CRC targets 150,000 patients per year diagnosed with stage II or III a/b colorectal cancer in the US, Europe and Australia excluding those unsuitable for chemotherapy due to age or health. Based on pricing of a competitor test with payor coverage the target market is valued at $1Billion. Ongoing development of the VASPfore platform in additional cancer types (e.g. breast, lung and prostate) will substantially increase market size. The total addressable market for the VASPfore platform is comprised of the 1.5 million patients per year diagnosed with an early/intermediate stage epithelial cancer in the US, Europe and Australia and is valued at $6.5 Billion.

PROGRAM

6:30: Cocktails and Dinner; there will be a cash bar and a special two-entrée buffet

8:00 David Zuzga PhD, CEO, will deliver the Company”s “Elevator” pitch to the group.

8:20: A panel consisting of Maria Maccecchini, Dennis Fujii and Caroline Hoedemaker will address three major issues crucial to helping the Company reach the next level. BioDetego has submitted the following questions:

BioDetego is a virtual company without full-time employees and is open-minded about the composition of itd eventual management team. Given the company’s planned next steps, what mix of experience and commitment (potentially draw from its founders, current advisory board members, or from outside the company) would be desirable to potential investors?
VASPfore has the potential to inform oncology clinical trials where enrolling cancer patients likely to relapse may increase the power of a study to determine treatment efficacy. How might BioDetego pursue and structure a co-development deal with a potential strategic partner?
Clinical development milestones, such as the completion of large clinical validation studies and expansion of the platform to additional cancers, represent significant value inflection points. How should these inflection points be integrated into an exit strategy which best manages investor risk and potential for return.

9:00: Q&A session

Remember to register: click on www.rxpcci.com and follow directions

Dinner price for members is a flat $40; Parking is free!

Lifetime dues for new members are still $100; join PCCI and your first dinner will be ON US!

Bring a friend and/or a business colleague! You know that our meetings a livelier and more interesting than ever.

The Embassy Suites Hotel provides an excellent facility, more room and a fine menu.

Every PCCI meeting is webcast. The webcast recording of the PCCI meetings will be posted on the PCCI website “rxpcci.com” and webcast live via the internet during the event.

Directions: Take Rt 202 to the Chesterbrook exit (that’s two exits South of the Devon exit), turn Right at the end of the Exit ramp and you’ll see the hotel at your Right. If you are going North on 202, get off at the Chesterbrook Exit and turn Left at the traffic light and drive back over Rt 202. You’ll see the hotel at your Right. Proceed to the traffic light and turn Right into the parking lot of the hotel. Their phone is: 610 647 6700.

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Use of Subtyping for Presurgical Breast Cancer Treatment Use

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Screening, Clinical Diagnostics, Curation, Evolutionary cognition, Explanatory, Gene Regulation and Evolution, Genome Biology, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Historical relevance, Molecular Genetics & Pharmaceutical, Technology Advance Assessment of, tagged breast cancer, genomic subtyping, prediction of long-term prognosis, treatment decisions on August 22, 2014| Leave a Comment »

Use of Subtyping for Presurgical Breast Cancer Treatment Use

Reporter, Reblog: Larry H Bernstein, MD, FCAP

More Accurate Identification of Molecular Subgroups May Better Guide Neo-adjuvant Treatment of Breast Cancer

By Susan Reckling
Posted: 8/19/2014 12:43:52 PM
Last Updated: 8/19/2014 12:43:52 PM

Key Points:

Although accurate classification of breast tumors by molecular subtype may guide the appropriate selection of therapy, conventional assessment methods lack standardization.
In the Neoadjuvant Breast Registry Symphony Trial of more than 400 women with breast cancer, standard assessment methods were compared with a novel 80-gene classifier known as BluePrint in combination with MammaPrint.
BluePrint molecular subtyping reclassified nearly one-fourth of tumors, with more responsive patients reassigned to the HER2 and basal categories and less responsive patients reassigned to the luminal category.

BluePrint in combination with MammaPrint molecular subtyping reclassified more than 20% of breast cancer patients into a different subgroup compared with conventional assessment, according to the results of the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). In Annals of Surgical Oncology, Whitworth et al reported that this reclassification of patients led to an improved distribution of response rates and a more accurate picture of which patients were likely to respond (or not respond) to neoadjuvant chemotherapy for breast cancer.

Selection of the appropriate therapy for a woman with breast cancer can be guided by accurate classification of the tumor by molecular subtype. Currently, however, conventional assessment methods such as immunohistochemistry and fluorescence in situ hybridization (FISH) lack standardization and the interpretation of test results differs among laboratories.

Thus, investigators have turned to other potentially more effective approaches to molecular subtyping. BluePrint, a novel molecular profile, is a multigene classifier, determining the mRNA levels of 80 genes. In combination with MammaPrint (risk stratification by multigene assays), BluePrint can classify patients with breast cancer into three subtypes based on functional molecular pathways: luminal (A or B), HER2, and basal.

Study Details

In the NBRST study, the investigators attempted to predict chemosensitivity in women with histologically proven breast cancer with the 80-gene BluePrint functional subtype profile vs conventional subtyping. Chemosensitivity was defined as pathologic complete response or the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resected specimen.

More than 400 women with breast cancer who had started or were scheduled to start neoadjuvant chemotherapy or hormone therapy took part in the multicenter NBRST study. All of them had definitive surgical resection. The age of study participants ranged from 22 to 80 years, with a median age of 52 years. Most of the patients (85%) had T2 or T3 tumors.

Patients who had undergone an excisional biopsy or axillary dissection or who had confirmed distant metastases were excluded from the study. Also, those who had received prior chemotherapy, radiotherapy, or endocrine therapy for breast cancer were ineligible for study participation.

Microarray analysis for the 80-gene BluePrint subtype and the 70-gene MammaPrint profiles was conducted at Agendia Laboratory, which was blinded to both clinical and pathologic data. BluePrint and MammaPrint analysis categorized the study patients as follows: 59 (14%) were luminal A, 153 (36%) were luminal B, 74 (17%) were HER2, and 140 (33%) were basal.

Reclassification to Different Molecular Subgroup

In total, 22% (94 of 426 patients) were reclassified in a different BluePrint/MammaPrint molecular subgroup compared with conventional subtyping. For instance, 37 of 211 patients (18%) of conventionally determined hormone receptor–positive/HER2-negative patients were reassigned by BluePrint as basal (35) or HER2-positive (2). In addition, 53 of 123 conventionally determined HER2-positive patients (43%) were reclassified as luminal (36) or basal (17).

As for response rates to neoadjuvant chemotherapy, the investigators reported an overall pathologic complete response rate of 25% (99 of 403 patients). Six percent of patients with luminal breast tumors had a pathologic complete response rate (2% for luminal A, 7% for luminal B).

More than half of the 74 patients with BluePrint-determined HER2-positive tumors had a pathologic complete response, which the investigators noted was significantly superior (P = .047) to the 38% of conventionally assigned HER2-positive patients.

Clinical Implications

Use of the multigene classifier BluePrint may assist oncologists in accurately identifying which patients with breast cancer may benefit from neoadjuvant chemotherapy and which ones are less likely to do so. According to the investigators, there are potential clinical implications for two particular groups of reassigned patients via BluePrint molecular subtyping: (1) those who were conventionally assigned as HER2-positive but not classified as such by BluePrint, and (2) those who were considered to have hormone receptor–positive/HER2-negative disease via conventional assessment but were reclassified to basal disease by BluePrint.

“This reclassification of patients leads to an improved distribution of response rates in the different subgroups of patients: a lower pathologic complete response rate for BluePrint luminal patients compared with [immumohistochemistry]/FISH-defined conventional luminal patients, with more responsive patients reassigned to the HER2 and basal categories,” concluded the investigators.

Pat Whitworth, MD, of the Department of Surgery, Nashville Breast Center, Nashville, Tennessee, is the corresponding author of the article in Annals of Surgical Oncology.

Lisette Stork-Sloots, MSc, and Femke A. de Snoo, MD, PhD, are employees of Agendia NV, Amsterdam, The Netherlands. The other authors disclosed no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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More on the Performance of High Sensitivity Troponin T and with Amino Terminal Pro BNP in Diabetes

Posted in Cardiovascular Research, Diabetes Mellitus, Diagnostic Immunology, Evidence-based decision-making, Frontiers in Cardiology and Cardiovascular Disorders, Immunodiagnostics, Proteomics, Quality Assurance, Systemic Inflammatory Response Related Disorders, Total error, Translational Research, Translational Science, tagged ACS, AMI, atrial natriuretic peptide, BNP, CHF, cTNI, cTnT, NT-proBNP, prediction of long-term prognosis on January 20, 2014| Leave a Comment »

More on the Performance of High Sensitivity Troponin T and with Amino Terminal Pro BNP in Diabetes

Writer and Curator: Larry H. Bernstein, MD, FCAP

UPDATED on 9/1/2019

Risk-Based Thresholds for hs-Troponin I Safely Speed MI Rule-Out

HISTORIC suggests benefit to patients, clinicians

PARIS — Using different cutoffs for high-sensitivity cardiac troponin I (hs-cTnI) testing based on risk accurately ruled out MI and sent patients home from the emergency department sooner without missing adverse cardiac events, the HISTORIC trial found.

In the stepped-wedge trial of over 30,000 consecutive patients, introduction of the risk-based approach reduced length of stay at the emergency department by over 3 hours compared with standard care (6.8 vs 10.1 hours, P<0.001), reported Nicholas Mills, MD, PhD, of the University of Edinburgh in Scotland.

And 74% of patients under the new pathway were discharged without requiring hospital admission versus 53% under standard protocols (adjusted risk ratio 1.57, 95% CI 1.34-1.83, P<0.001).

For the primary safety endpoint, 2.5% of patients in the standard group died from cardiac causes or had an MI at 12 months post-discharge versus 1.8% of those in the early rule-out group (adjusted OR 1.02, 95% CI 0.74-1.40).

“Adoption of this approach will have major benefit for both patients and healthcare providers,” said Mills during a late-breaking press briefing at the 2019 European Society of Cardiology (ESC) congress.

For example, many patients will need only a single troponin test under the algorithm to lead to a decision on admission, he noted, which could have “absolutely enormous” cost savings.

Primary Source

European Society of Cardiology

Source Reference: Mills NL, et al “High-sensitivity cardiac troponin at presentation to rule out myocardial infarction (HISTORIC): A stepped-wedge cluster-randomised controlled trial” ESC 2019; Abstract 2309.

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/81926?xid=nl_mpt_ACC_Reporter_2019-09-01&eun=g5099207d2r

UPDATED on 8/7/2018

Siemens’ high-sensitivity Troponin I (TnIH) assays got FDA clearance for use in diagnosing acute myocardial infarction. (Cardiovascular Business) The first high-sensitivity Troponin T test was cleared last year, as MedPage Today reported.

SOURCE

https://www.medpagetoday.com/cardiology/prevention/74423?xid=nl_mpt_cardiobreak2018-08-06&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Ca

This is the final up to date review of the status of hs troponin T (or I) with or without the combined use of the Brain Type Natriuretic Peptide or its Amino Terminal peptide precursor. In addition, a new identification of the role of the Atrial Natriuretic Peptide has been reported with respect to arrythmogenic activity. On the one hand, the diagnostic value of the NT-proBNP has been seen as disappointing, in part because of the question of what information is gained by the test in overt known congestive heart failure, and in part because of uncertainty about following the test during a short hospital stay. At least, this is the view of this reviewer. However, in the last several years there has been an emphasis on the value this test adds to prediction of adverse outcomes. In addition, there has been a hidden nvariable that has much to do with the original reference values that were established for age ranges, without any consideration of pathophysiology that might affect the values within those ranges, leading one to consider values in an aging population as normal, that might well be high. Why is this? Aging patients are more likely to have hypertension, and also the onset of type-2 diabetes mellitus, with cardiovascular disease consequences. Type-2 diabetes mellitus (T2DM), for instance, is associated with insulin resistance and also fat gain with generation of adipokines, but the is also a hyalinization of insulin forming beta-cells of the pancreas, and there is hyalinization of glomeruli (glomerulosclerosis) and afferent arteriolonephrosclerosis with expected decline in glomerular filtrattion rate and hypertension as well. Of course, this is also associated with hepatosteatosis. Nevertheless, a reference range is established that takes none of this pathophysiology into account. While a more reasonable approach has been pointed out, there has been no followup in the literature.

On the other hand, there has been much confusion over the restandardization of a high sensitivity troponin I or T test (hs-Tn(I or T). The reference range declines precipitously, and there is a good identification of patients who are for the most part disease free, but there is no delineation of patients who are at high risk of acute coronary syndrome with plaque rupture, vs a host of other cardiovascular conditions. These have no relationship to plaque rupture, but may be serious and require further evaluation. The question then becomes whether to admit for a hospital stay, to refer to clinic after an evaluation in the ICU without admission, or to do an extensive evaluation in the emergency department overnight before release for followup. There is still another dimension of this that has to do with prediction of outcomes using hs-Tn(s) with or without the natriuretic peptides. Another matter that is not for discussion in this article is the underutilization of hs-CRP. Originally used for a marker of sepsis in the 1970s, it has come to be tied in with identification of an ongoing inflammatory condition. Therefore, the existence of a known inflammatory condition in the family of autoimmune diseases, with one exception, might make it unnecessary.

The discussion is broken into three parts:

Part 1. New findings on the troponins.
Part 2. The use of combined hs-Tn with a natriuretic peptide (NT-proBNP)
Part 3. Atrial natriuretic peptide

Part 1. New findings on the troponins.

Troponin: more lessons to learn

C Liebetrau,HM Nef,andCW.Hamm*

KerckhoffHeartandThoraxCenter;DepartmentofCardiology,BadNauheim,
Germany; (GermanCentreforCardiovascularResearch),partnersite
RheinMain,BadNauheim, Germany; and UniversityofGiessen,Medizinische
KlinikI,KardiologieundAngiologie,Giessen,Germany
European Hear tJournal
http://dx.doi.org/10.1093/eurheartj/eht357This editorial refers to ‘Risk stratiﬁcation in patients with acute chest pain
using three high-sensitivity cardiac troponin assays’,
by P. Haafetal. http://dx.doi.org/10.1093/eurheartj/eht218Cardiac troponin entered our diagnostic armamentarium 20 years ago and –
unlike any other biomarker –

is going through constant expansion in its application.

Troponin started out as a marker of risk in unstable angina’, then was used

as gold standard for risk stratiﬁcation and therapy guiding in acute coronary syndrome
served further to redeﬁne myocardial infarction, and
has also become a risk factor in apparently healthy subjects.

The recently introduced high-sensitivity cardiac troponin (hs-cTn) assays

have not only expanded the potential of troponins, but
have also resulted in a certain amount of confusion
- among unprepared users.

After many years troponins were accepted as the gold standard in

patients with chest pain by
classifying them into troponin-positive and
- troponin-negative patients.

The new generation of hs-cTn assays has

improved the accuracy at the lower limit of detection and
provided incremental diagnostic information especially
- in the early phase of myocardial infarction.

Moreover, low levels of measurable troponins

unrelated to ACS have been associated with
- an adverse long-term outcome.

Several studies demonstrated that

these low levels of cardiac troponin measureable
- only by hs-Tn assays
are able to predict mortality in patients with ACS
as well as patients with assumed
- stable coronary artery disease.

Furthermore, hs-cTn has the potential

to play a role in the care of patients
- undergoing non-cardiac surgery.

The additional determination of hs-cTn

improves risk stratification despite
established risk scores providing both diagnosis and
for prognosis prediction in chest pain patients.

The daily clinical challenge in using the highly sensitive assays is to

interpret the troponin concentrations, especially
in patients with concomitant diseases
- independently from myocardial ischaemia
inﬂuencing cardiac troponin concentrations
(e.g. chronic kidney disease, or stroke).

The troponin test lost its ‘pregnancy test’ quality with the different users.
Different opinions exist on

the change of hs-cTn levels compared to simple ‘positive–negative’ interpretation
and thereby makes diagnosis ﬁnding more complex than before.

This uncertainty probably has the paradigm that

serial measurements of troponins are necessary, and also
- boosted the number of diagnoses of ACS and
- invasive diagnostic procedures in some locations.

This is more than understandable, with acute chest pain using

three high-sensitivity cardiac troponins with their respective baseline value
- before the diagnosis of acute myocardial infarction (AMI) can be made.

What is a relevant change in concentrations compatible with acute myocardial necrosis and

what is only biological variation for the speciﬁc biomarker and assay?

Changes in serial measurements between 20% and 200% have been debated, and
the discussion is ongoing. Furthermore, it has been proposed that

absolute changes in cardiac troponin concentrations
- have a higher diagnostic accuracy for AMI
compared with relative changes, and

it might be helpful in distinguishing AMI from other causes of cardiac troponin elevation.

Do we obtain any helpful directives from experts and guidelines for our daily practice?
Foreseeing this dilemma, the 2011 European Society of Cardiology (ESC) Guidelines

on non ST-elevation ACS acted.
Minor elevations of troponins were accepted as hs-cTn values in the ‘grey zone’.

This was and still is the rule, but

the ESC provided a general algorithm on how to manage patients with limited data.

The ‘Study Group on Biomarkers in Cardiology’ suggested

a rise of 50% from the baseline value at low concentrations.

However, this group of experts could also not ﬁnd a substitute for the missing data

needed to validate the proposed recommendation.

The story is just too complex:

different troponin assays with
different epitope targets,
different patient populations,
different sampling protocols,
different follow-up lengths, and much more.

Therefore, any study that helps us to see better through the fog is welcome here.

Haaf et al. have now presented the results of their study of

different hs-cTn assays
(hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; and hs-cTnI, Siemens)
- with respect to the -outcome of patients with acute chest pain.

The authors examine 1117 consecutive patients presenting with acute chest pain.
[340 patients with ACS (30.5%)] from the Advantageous Predictors of Acute Coronary Syndrome
Evaluation (APACE) study. Blood was collected

directly on admission and
serially thereafter at 2, 3, and 6h.

Eighty-two patients (7.3%) died during the 2-year follow-up. The main ﬁnding of the study is that

hs-cTnT predicts mortality more accurately than the hs-cTnI assays,
-that a single measurement is sufﬁcient
challenges causes of cardiac troponin elevation.

These results of APACE remain in contrast to recent ﬁndings from a GUSTO IV cohortof 1335 patients with ACS (Table1).

Table1 Studies investigating high sensitivity troponins for long-term prognosis

Variable APACE (n 5 1117) GUSTO IV (n 5 1335) PEACE (n 5 3567)

………………………………………………………………………………………………………………………………………………………….

Patient cohort Unstable Unstable Stable

Blood sampling On admission,1,2,3,6h 48h after
study randomization Before randomization

No. of patients with detection limit 883 (79.1%) UKN UKN

No. of patients with hs-cTnT.
99thpercentile 401 (35.9%) 1015 (76%) 395 (10.9%)

No. of patients with hs-cTnI (Abbott).
detection limit UKN UKN 3567 (98.5%)

No.of patients with hs-cTnI (Abbott).
99th percentile UKN 988(74%) 105 (2.9%)

No. of patients with NSTEMI 170 (15.2%) 100 (100%) 0 (0%)

Follow-up 24 months 12 months 5.2 years

Non-fatal AMI UKN UKN 209 (5.9%)

Mortality or primary endpoint 82 (7.3%) 119(8.9%) 203 (5.7%)

………………………………………………………………………………………………………………………………………………………….

Key ﬁndings cTnT better than cTnI cTnI ¼cTnT cTnI better than cTnT

Single cTn sample sufﬁcient

AMI, acute mycordial infaction; cTn, cardiac tropononin; NSTEMI ,non-ST-elevation myocardial infarction; UKN, unknown

NSTEMI deﬁned in the GUSTO IV trial:

one or more episodes of angina lasting ≥ 5min,
within 24h of admission and
either a positive cardiac TnT or I test
(above the upper limit of a normal for the local assay; during the years 1999 and 2000)
or ≥ 0.5 mm of transient or persistent ST-segment depression.

the prognostic capacity of four different sensitive cardiac troponin assays were compared

hs-cTnT; Roche Diagnostics,
cTnI and hs-cTnI;
Abbott Diagnostics, and
Acc-cTnI; Beckman-Coulter.

In total, 119 patients (8.9%) died during the 1-year follow-up. Looking at their

receiver operating characteristic curve (ROC) analyses,
there were only negligible diffferences
- in the area under the curves between the assays.

Contrasting results have also been reported in patients(n 1/4 3.623)

with stable coronary artery disease and preserved systolic left ventricular function

from the PEACE trial (Table1).

During a median follow-up period of 5.2 years,

there were 203 (5.6%) cardiovascular deaths or
ﬁrst hospitalization for heart failure.

Concentrations of hs-cTnI (Abbott Diagnostics) at or above

the limit of detection of the assay were measured in 3567 patients (98.5%), but
concentrations of hs-cTnI at or above the gender-speciﬁc 99th percentile
- were found in only 105 patients (2.9%).

This study revealed that

there was a strong and graded association
between increasing quartiles of hs-cTnI concentrations and
the risk for cardiovascular death or heart failure.

Hs-cTnI provided incremental prognostication information

over conventional risk markers and
other established cardiovascular biomarkers,
including hs-cTnT.

In contrast to the APACE results, only hs-cTnI, but

no ths-cTnT, was signiﬁcantly
associated with the risk for AMI.

Is there a real difference between cardiac troponin T and cardiac troponin I

in predicting long term prognosis?

The question arises of whether there is a true clinically relevant

difference between cTnT and cTnI.

Given the biochemical and analytical differences,the two

troponins display rather similar serum proﬁles during AMI.

While minor biological differences between cTnT and cTnI are

apparently not relevant for diagnosis
and clinical management in the acute setting of ACS.

This is a provocative theory, but appears premature in our opinion.
Above all, the results of the current study appear

too inconsistent to allow such conclusions.

In the present study, hs-cTnT (Roche Diagnostics) outperformed

hs-cTnI (Siemens and Beckman-Coulter) in terms of
very long term prediction of cardiovascular death and
- heart failure in stable patients.

We don’t know how hs-cTnI from Abbott Diagnostics

performs in the APACE consort.

The number of patients and endpoints provided

by the APACE registry are rather low.
The results could, therefore, be a chance finding.

It is far too early to favour one high sensitivity assay over the other. The findings need confirmation.

Implications for clinical practice

There is no doubt that high-sensitivity assays

are the analytical method of choice
- in terms of risk stratiﬁcation in patients with ACS.

What is new?
A single measurement of hs-cTn seems to be adequate

for long-term risk stratiﬁcation in patients without AMI.

However, the question of which troponin might be preferable

for long-term risk stratification remains unanswered.

Part 2. ability of high-sensitivity cTnT and NT pro-BNP to predict cardiovascular events and death in patients with T2DM

Hillis GS; Welsh P; Chalmers J; Perkovic V; Chow CK; Li Q; Jun M; Neal B; Zoungas S; Poulter N; Mancia G; Williams B; Sattar N; Woodward M
Diabetes Care. 2014; 37(1):295-303 (ISSN: 1935-5548)

OBJECTIVE

Current methods of risk stratification in patients with

type 2 diabetes are suboptimal.

The current study assesses the ability of

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and
high-sensitivity cardiac troponin T (hs-cTnT)

to improve the prediction of cardiovascular events and death in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease:

Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

RESULTS

Seven hundred nine (18%) patients experienced a

major cardiovascular event

(composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and

706 (18%) died during a median of 5 years of follow-up.

In Cox regression models, adjusting for all established risk predictors,

the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and
the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were
- 1.97 (95% CI 1.73, 2.24) and
- 1.52 (95% CI 1.37, 1.67), respectively.

The addition of either marker improved 5-year risk classification for cardiovascular events
(net reclassification index in continuous model,

39% for NT-proBNP and 46% for hs-cTnT).

Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted.
The combination of both markers provided optimal risk discrimination.

CONCLUSIONS

NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the

risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.

PreMedline Identifier: 24089534

Part 3. M-Atrial Natriuretic Peptide

M-Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure:
Differential Actions of 2 cGMP Activating Therapeutics.

Paul M McKie, Alessandro Cataliotti, Tomoko Ichiki, S Jeson Sangaralingham, Horng H Chen, John C Burnett
Journal of the American Heart Association 01/2014; 3(1):e000206. http://dx.doi.org/10.1161/JAHA.113.000206
Source: PubMed

ABSTRACT

Systemic hypertension is a common characteristic in

acute heart failure (HF).

This increasingly recognized phenotype

is commonly associated with renal dysfunction and
there is an unmet need for renal enhancing therapies.

In a canine model of HF and acute vasoconstrictive hypertension

we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP),
a novel particulate guanylyl cyclase (pGC) activator, and
nitroglycerin, a soluble guanylyl cyclase (sGC) activator.

HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II
infusion. We characterized the cardiorenal and humoral actions