The goal of this proposal is to implement new strategies in personalized risk assessment for heart failure progression and sudden cardiac death (SCD) using a sequential algorithm involving ECG and cardiac MRI analyses in combination with conventional and newly emerging risk-stratification methods. While prevention of heart failure progression and SCD in patients of indeterminate risk represents one of the most challenging issues in contemporary cardiology, there has been little progress in reducing the incidence of heart failure and SCD mortality. Furthermore, current risk-stratification methods that focus on LV dysfunction and electrophysiological metrics lack the sensitivity and specificity needed for individualized care. Here we assess myocardial damage by applying novel automated ECG based QRS scoring combined with the detection of heterogeneity in myocardial structure and viability with contrast-enhanced MRI. We have validated the ECG QRS-scoring algorithm against high resolution scar quantification by MRI, thus demonstrating its potential utility in identifying individuals who should undergo detailed infarct heterogeneity studies by MRI for further risk stratification. Thus, in Phase I we apply the two modalities sequentially in combination with existing markers to refine development of an algorithm that will then be used to address feasibility and accuracy of the approach in a large (n>2,000) multi-center analysis during Phase II, where technological, logistical and intellectual advances refined in Phase I will be implemented at 4 additional institutions. Marker associations, cardiac events and statistical outcomes will be analyzed via the centralized computer system provided by the NIH Cardiovascular Research GRID resource (CVRG) at our institution. Based on preliminary data, we anticipate that this new combined diagnostic approach will discriminate patients who harbor previously undetected high risk for heart failure progression as well as SCD mortality susceptibility that is not detectable using current strategies. Evaluation of ancillary genetic- and bio-markers during Phase II will provide additional prognostic information useful for individualized risk assessment.

Public Health Relevance

This proposal addresses two major public health challenges in cardiology: improved identification and risk stratification of patients for 1) sudden cardiac death and 2) heart failure progression and mortality. Focus is placed on non-invasive approaches relevant to evaluation of specific individuals to improve drug and device targeting using new and existing therapies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory Grants (P20)
Project #
5P20HL101397-02
Application #
8014913
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (F1))
Program Officer
Desvigne-Nickens, Patrice
Project Start
2010-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2011
Total Cost
$601,474
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Tiffany Win, Theingi; Ambale Venkatesh, Bharath; Volpe, Gustavo J et al. (2015) Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance: The PRIMERI Study. Heart Rhythm 12:155-62
Magalhaes, Tiago A; Lima, Joao A C (2014) Defining the flow-limiting stenosis noninvasively for management of patients with coronary artery disease. JACC Cardiovasc Interv 7:79-80
Tereshchenko, Larisa G; Rizzi, Patricia; Mewton, Nathan et al. (2014) Infiltrated atrial fat characterizes underlying atrial fibrillation substrate in patients at risk as defined by the ARIC atrial fibrillation risk score. Int J Cardiol 172:196-201
Murthy, Sindhoora; Rizzi, Patricia; Mewton, Nathan et al. (2014) Number of P-wave fragmentations on P-SAECG correlates with infiltrated atrial fat. Ann Noninvasive Electrocardiol 19:114-21
Strauss, David G; Mewton, Nathan; Verrier, Richard L et al. (2013) Screening entire health system ECG databases to identify patients at increased risk of death. Circ Arrhythm Electrophysiol 6:1156-62
Wu, Katherine C (2012) Assessing risk for ventricular tachyarrhythmias and sudden cardiac death: is there a role for cardiac MRI? Circ Cardiovasc Imaging 5:2-5
Mewton, Nathan; Liu, Chia Ying; Croisille, Pierre et al. (2011) Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol 57:891-903