Dilated cardiomyopathy | Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Posts Tagged ‘Dilated cardiomyopathy’

genetics, myocardium, and heart rhythm

Posted in Acute Myocardial Infarction, Anemia in CVD Patients, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cardiomyopathy, Cardiovascular Research, Clinical Diagnostics, Computational Biology/Systems and Bioinformatics, Curation, Diabetes Mellitus, Disease Biology, Electrophysiology, Epigenetics and Cardiovascular Risks, Frontiers in Cardiology and Cardiovascular Disorders, Genomic Testing: Methodology for Diagnosis, Innovations, Myocardial Ischemia, Neurohumoral Transmission, Nitric Oxide in Health and Disease, tagged Atrial fibrillation, Diabetes, Dilated cardiomyopathy, gene signatures, Heart Failure, heart rhythm measurement, heart rhythm variability on September 9, 2014| Leave a Comment »

Larry H Bernstein, MD, FCAP, Curator

Leaders in Pharmaceutical Intelligence

Association of heart rate variability and inflammatory response in patients with cardiovascular diseases: current strengths and limitations
V Papaioannou, I Pneumatikos and N Maglaveras
Front Phys 2013.
http://dx.doi.org:/10.3389/fphys.2013.00174

A few clinical studies have assessed the possible inter-relation between neuro-autonomic output, estimated with heart rate variability analysis, which is the variability of R-R in the electrocardiogram, and different inflammatory biomarkers, in patients suffering from stable or unstable coronary artery disease (CAD) and heart failure. Moreover, different indices derived from heart rate signals’ processing, have been proven to correlate strongly with severity of heart disease and predict final outcome. In this review article we will summarize major findings from different investigators, evaluating neuro-immunological interactions through heart rate variability analysis, in different groups of cardiovascular patients. We suggest that markers originating from variability analysis of heart rate signals seem to be related to inflammatory biomarkers.
Atrial Natriuretic Peptide Frameshift Mutation in Familial Atrial Fibrillation

DM. Hodgson-Zingman, ML. Karst, LV. Zingman, DM. Heublein, et al.
N Engl J Med. 2008 July 10; 359(2): 158–165 http://www.nejm.org/doi/full/10.1056/NEJMoa0706300

We mapped an atrial fibrillation locus to chromosome 1p36-p35 and identified a heterozygous frameshift mutation in the gene encoding atrial natriuretic peptide. Circulating chimeric atrial natriuretic peptide (ANP) was detected in high concentration in subjects with the mutation, and shortened atrial action potentials were seen in an isolated heart model, creating a possible substrate for atrial fibrillation. This report implicates perturbation of the atrial natriuretic peptide–cyclic guanosine monophosphate (cGMP) pathway in cardiac electrical instability.
Impact of anemia on clinical outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry.
M Puurunen, T Kiviniemi, W Nammas, A Schlitt, A Rubboli, K Nyman, et al.
BMJ Open 2014; 4:e004700.
http://dx.doi.org:/10.1136/bmjopen-2013-004700

The study adds to our knowledge on the prevalence and impact of anemia in patients with AF undergoing PCI and thus requiring combination antithrombotic medication. It shows that anemia is a frequent finding and that even mild anemia has an adverse impact on outcome.
Atrial Natriuretic Peptide Single Nucleotide Polymorphisms in Patients with Nonfamilial Structural Atrial Fibrillation.
P Francia, A Ricotta, A Frattari, R Stanzione, A Modestino, et al.
Clinical Medicine Insights: Cardiology 2013:7 153–159
http://dx.doi.org:/10.4137/CMC.S12239

We report lack of association between the rs5065 and −G664C ANP gene SNPs and AF in a Caucasian population of patients with structural AF. Further studies will clarify whether these or other ANP gene variants affect the risk of different subpheno-types of AF driven by distinct pathophysiological mechanisms.
Gene Expression and Genetic Variation in Human Atria.

H Lin, EV. Dolmatova, MP. Morley, KL. Lunetta, et al.
Heart Rhythm HRTHM5533.
http://dx.doi.org/10.1016/j.hrthm.2013.10.051

We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function.
A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a SNP at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.

Global Left Atrial Strain Correlates with CHADS2 Risk Score in Patients with Atrial Fibrillation
SK. Saha, PL. Anderson, G Caracciolo, A Kiotsekoglou, S Wilansky, et al.

J Am Soc Echocardiogr 2011;24:506-12.
http://dx.doi.org:/10.1016/j.echo.2011.02.012

Global longitudinal LA strain was reduced in patients with AF compared with controls (P < .001) and was a predictor of high risk for thromboembolism (CHADS2 score > 2; odds ratio, 0.86; P = .02). LA strain indexes showed good interobserver and intraobserver variability. In sequential Cox models, the prediction of hospitalization and/or death was improved by addition of global LA strain and indexed LA volume to CHADS2 score (P = .003).

Time and Frequency Domain Analysis of Heart Rate Variability and their Correlations in Diabetes Mellitus.
PTA Seyd, VIT Ahamed, J Jacob, P Joseph K.
Int Biol and Life Sci 2008; 4(1).
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.307.6260

In this paper, changes in ANS activity are quantified by means of frequency and time domain analysis of R-R interval variability. Electrocardiograms (ECG) of 16 patients suffering from DM and of 16 healthy volunteers were recorded. Frequency domain analysis of extracted normal to normal interval (NN interval) data indicates significant difference in very low frequency (VLF) power, low frequency (LF) power and high frequency (HF) power, between the DM patients and control group. Time domain measures, standard deviation of NN interval (SDNN), root mean square of successive NN interval differences (RMSSD), successive NN intervals differing more than 50 ms (NN50 Count), percentage value of NN50 count (pNN50), HRV triangular index and triangular interpolation of NN intervals (TINN) also show significant difference between the DM patients and control group.

Power Spectral Density of the RR interval of a 55 year old healthy volunteer

Power Spectral Density of the RR interval of a 62 year old woman suffering from diabetes for the last 15 years.

Time domain and frequency domain analysis of the RR interval variability of diabetic and normal subjects shows that there is significant difference in these measures for DM patients with respect to normal subjects. Variation of the HRV parameters indicates changes in ANS activity of DM patients. This can provide valid information regarding autonomic neuropathy in people with diabetes. It may be noted that these methods can detect changes before clinical signs appear.

Quantification of Heart Rate Variability: A Measure based on Unique Heart Rates
VIT Ahamed, P Dhanasekaran, A Naseem, NG Karthick, TKA Jaleel, Paul K

It is established that the instantaneous heart rate (HR) of healthy humans keeps on changing. Analysis of heart rate variability (HRV) has become a popular non invasive tool for assessing the activities of autonomic nervous system. Depressed HRV has been found in several disorders, like diabetes mellitus (DM) and coronary artery disease, characterised by autonomic nervous dysfunction. A new technique, which searches for pattern repeatability in a time series, is proposed specifically for the analysis of heart rate data. These set of indices, which are termed as pattern repeatability measure and pattern repeatability ratio are compared with approximate entropy and sample entropy.

Cardiovascular autonomic neuropathy in patients with diabetes mellitus
International Journal of Pharma and Bio Sciences
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.178.2974

The cardioautonomic reflexes of 82 diabetic subjects and 40 age and sex matched healthy controls were studied using blood pressure and heart rate variation in response to standing, deep breathing, isometric exercise, cold pressor test and determination of QTc interval. Among the 82 patients, 68 patients were found to have cardiac autonomic neuropathy (CAN). Results showed that diabetics had significantly impaired cardioautonomic reflexes compared to non-diabetics, which increases with the duration of diabetes. Out of 68 patients with CAN, QTc prolongation was observed in 64 patients. In conclusion the autonomic nervous system integrity is appeared to be greatly affected by diabetes mellitus and the degree of impairment was dependent on duration of the disease.

Prognostic Value of Heart Rate Variability Analysis in Patients with Depressed Left Ventricular Function Irrespective of Cardiac Rhythm
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.377.9244
M Sosnowski, Pw Macfarlane, R Parma, J Skrzypek-wanha, M Tendera

A new index of heart rate variability – HRF Fraction – was developed and its value for risk stratification was evaluated in 480 patients with coronary heart disease. The main purpose to introduce the HRVF was to overcome one of the most important constraints – cardiac arrhythmia, especially atrial fibrillation – that limits use of HRV measurement as a routine clinical tool. In 384 patients with sinus rhythm (SR) and 96 with AF HRV measurements from 24h ambulatory ECG were performed. Patients were followed for a median period of 28 months. The HRV indices in those who died were compared to those who survived. Authors found that HRV Fraction and- among standard time-domain indices- only SDANN, possessed properties that allow HRV measurement to be applied for risk stratification studies in unselected population of patients with cardiac arrhythmia.

Short- and long-term reproducibility of heart rate variability in patients with long-standing type I diabetes mellitus.
Burger AJ¹, Charlamb M, Weinrauch LA, D’Elia JA
Am J Cardiol. 1997 Nov 1;80(9):1198-202.
http://www.ncbi.nlm.nih.gov/pubmed/9359550

Using Pearson correlation, the time domain indicators of parasympathetic activity demonstrated very strong correlations at 3 and 6 months compared with baseline, with good correlations at 1 year. The average SD of all 5-minute RR intervals maintained a very strong correlation for the entire year (r >0.94). In the frequency domain, the measures of parasympathetic and sympathetic activity maintained a solid correlation for the entire study period. Reproducibility of HRV was also examined using repeated-measures analysis of variance. The time and frequency domain parameters demonstrated very little variation over the study period of 12 months. Thus, our investigation demonstrated that HRV in long-term diabetics using 24-hour ambulatory recordings is abnormal and reproducible over a 12-month interval; very little variation in all HRV parameters, especially in parameters of parasympathetic activity, occurred during the study period.

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Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF) and Midwall Fibrosis: Decisions on Replacement using late gadolinium enhancement cardiovascular MR (LGE-CMR)

Posted in Frontiers in Cardiology and Cardiovascular Disorders, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Origins of Cardiovascular Disease, Uncategorized, tagged Dilated cardiomyopathy, Ejection Fraction, Heart Failure, Interventricular septum, JAMA, LVEF, Royal Brompton Hospital, sudden cardiac death on March 10, 2013| 11 Comments »

Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF) and Midwall Fibrosis: Decisions on Replacement using late gadolinium enhancement cardiovascular MR (LGE-CMR)

Reporter: Aviva Lev-Ari, PhD, RN

2 imaging studies offer intrigue but clinical gain remains in doubt

By Candace Stuart

Mar 06, 2013

Two separate studies edged delayed-enhancement cardiovascular MRI toward the clinical equivalent of home plate, but neither scored a run. The studies and an accompanying editorial were published March 6 in the Journal of the American Medical Association.

Ankur Gulati, MD, of Royal Brompton Hospital in London, and colleagues assessed the prognostic value of midwall fibrosis with late gadolinium enhancement cardiovascular MR (LGE-CMR) to predict adverse outcomes for patients with dilated cardiomyopathy. This condition may lead to progressive heart failure and sudden cardiac death (SCD); consequently, risk stratification beyond assessments based on left ventricular ejection fraction (LVEF) may help physicians tailor management plans, including selecting patients for implantable cardioverter-defibrillators (ICDs).

“Most patients who experience SCD do not have severely reduced LVEF, and many patients with significant impairment of LVEF may still be at low risk for SCD,” they wrote. About one-third of these patients have a characteristic midwall pattern of replacement fibrosis detected by LGE-CMR, which the authors suggested might be a predictor of mortality and SCD.

To test that hypothesis, they designed a prospective longitudinal study that enrolled 472 consecutive patients with dilated cardiomyopathy who were referred to their hospital between 2000 and 2008. The patients underwent LGE-CMR to evaluate the presence and extent of midwall fibrosis, with follow-up through December 2011. The primary endpoint was all-cause mortality and the secondary endpoints were cardiovascular mortality or heart transplantation, the composite of SCD or aborted SCD and the composite of heart failure, heart failure hospitalization and heart transplant.

Two independent readers who were blinded to clinical data assessed the presence of midwall fibrosis and an experienced operator quantified the extent of fibrosis. They verified deaths through national resources, death certificates and communications with physicians and families.

Patients had a mean LVEF of 37 percent and were followed for a median duration of 5.3 years. Thirty percent had midwall fibrosis with a median extent of 2.5 percent. The mortality rate for patients with midwall fibrosis was 26.8 percent compared with 10.6 percent for patients without midwall fibrosis and the presence of midwall fibrosis was associated with a higher risk of cardiovascular mortality or transplantation. Patients with midwall fibrosis had higher rates of SCD or aborted SCD (29.6 percent vs. 7 percent) and higher rates of the heart failure composite (25.4 percent vs. 11.2 percent).

Adding midwall fibrosis to a risk model decreased the mortality risk for patients with an LVEF of 35 percent and no midwall fibrosis from 12.7 percent to 9.4 percent and increased mortality risk for patients with midwall fibrosis from 12.7 percent to 19.9 percent. Twenty-nine percent of patients were correctly reclassified with the addition of midwall fibrosis status, Gulati et al determined.

“The addition of midwall fibrosis to LVEF resulted in significant improvements in risk reclassification for both all-cause mortality and the arrhythmic composite,” they wrote. “Our findings suggest that detection and quantification of midwall fibrosis by LGE-CMR may represent useful markers for the risk stratification of death, ventricular arrhythmia and HF [heart failure] for patients with dilated cardiomyopathy.”

They added that the information provided by imaging could help in identifying patients at high risk who would benefit from ICD implantation.

In the second study, Dipan J. Shah, MD, of the Duke Cardiovascular Magnetic Resonance Center in Durham, N.C., and colleagues evaluated patients with regional myocardial wall thinning to assess if they have minimal or no scarring using LGE-CMR. They suggested that such regions might represent viable myocardium. They enrolled 1,055 patients with coronary artery disease who underwent LGE-CMR imaging at three centers between 2000 and 2008.

The study was divided into three parts: first, to determine the prevalence of regional thinning; second, to evaluate the prevalence of limited scar burden (less than 50 percent) in thinned myocardium; and third, to evaluate the relationship between scar burden and functional burden and tissue remodeling in patients who received coronary revascularization.

Nineteen percent of the patients had myocardial wall thinning with thinning of a substantial (a mean of 34 percent) portion of the left ventricle (LV). Of those with wall thinning, 18 percent had scarring of less than 50 percent.

Seventy-two percent of patients underwent revascularization. Shah et al reported inverse relationships between the extent of scarring and contractile improvement after revascularization as well as myocardial remodeling, with only those patients with limited scar burden showing improvement. Based on those findings, they suggested that myocardial thinning may be reversible.

“[W]e have shown that the myocardial wall may thin and revert back to full thickness as long as limited scarring is present,” they wrote. “These results indicate that the end stage of remodeling is better determined by tissue composition (i.e., scarring) rather than any set level of morphological changes to the LV cavity or LV wall.”

In an accompanying editorial, Deepak K. Gupta, MD, Raymond Y. Kwong, MD, MPH, and Marc A. Pfeffer, MD, PhD, all of Brigham and Women’s Hospital in Boston, pointed to limitations in both studies. As a single center study using low-risk patients, Gulati et al’s findings may not apply to those patients who would most benefit from risk stratification, they wrote, and the study by Shah et al was subject to referral and selection bias.

“Collectively, these and other studies demonstrate that CMR with LGE imaging adds to the practitioner’s armamentarium for assessment of cardiac structure and function and augments diagnostic and prognostic capabilities,” the editorial writers offered.

But determining which patients to evaluate remained a challenge. “At this point, for the practicing physician, the incremental information gained from CMR with LGE imaging from these two studies, albeit novel and supportive, is not yet sufficient to alter clinical practice guidelines,” they concluded.

http://www.cardiovascularbusiness.com/topics/imaging/2-imaging-studies-offer-intrigue-clinical-gain-remains-doubt?page=0%2C0