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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 9  |  Issue : 4  |  Page : 198-204

Relation between Fragmented Electrocardiogram and Myocardial Reserve in Patients with Cardiac Syndrome X


1 Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 National Heart Center, Tajoura, Tripoli, Libya

Date of Web Publication11-Mar-2020

Correspondence Address:
Dr. Islam Elsayed Shehata
Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig 44519
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JICC.JICC_51_19

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  Abstract 


Background: We hypothesized that fragmented QRS (fQRS) is an early marker of myocardial involvement in patients with cardiac syndrome X (CSX) which had updated term “Microvascular angina (MVA)”. Therefore, we aimed to investigate the possible relationship between fQRS and myocardial reserve in patients with MVA. Patients and Methods: A comparative cross-section study was conducted on 89 patients with typical angina symptoms, positive exercise treadmill test, and normal coronary angiography. All patients were subjected to history taking, electrocardiogram, echocardiography, dobutamine stress echocardiography, coronary angiography and measurement of body mass index, blood pressure and serum lipid profile. Results: The prevalence of fQRS in patients with MVA was 61%; there were nonsignificant difference in baseline echocardiography left ventricular mass, dimensions, and ejection fraction (EF%) between patients with and without fQRS; on the other hand, patients with fQRS showed a significant decrease in myocardial reserve at dobutamine stress echocardiography, and significant decrease in values of stroke volume and EF in comparison with patients without fQRS, fQRS was inversely correlated with cardiac output, stroke volume, EF as well as cardiac reserve; furthermore, number of leads with fQRS had a significant positive correlation with degree of reduction in cardiac reserve. Conclusion: In MVA patients, fQRS was correlated with reduced cardiac reserve; it has an important clue for microvascular and cardiac contractile dysfunction in these patients. Further follow-up data should be done on a large scale to show how to follow and treat those patients.

Keywords: Cardiomyopathy, contractile reserve, fragmented QRS, syndrome-X, microvascular angina


How to cite this article:
Shehata IE, A. Belgasem AM, Mahfouz RA, Tawfik OF. Relation between Fragmented Electrocardiogram and Myocardial Reserve in Patients with Cardiac Syndrome X. J Indian coll cardiol 2019;9:198-204

How to cite this URL:
Shehata IE, A. Belgasem AM, Mahfouz RA, Tawfik OF. Relation between Fragmented Electrocardiogram and Myocardial Reserve in Patients with Cardiac Syndrome X. J Indian coll cardiol [serial online] 2019 [cited 2020 Apr 6];9:198-204. Available from: http://www.joicc.org/text.asp?2019/9/4/198/280350




  Introduction Top


Cardiac syndrome X (CSX) which had updated term “Microvascular Angina (MVA)” is a typical angina-like chest pain with evidence of myocardial ischemia in the absence of flow-limiting stenosis on coronary angiography. It is characterized by a decrease in coronary flow reserve without epicardial artery stenosis; MVA is a heterogeneous entity, both clinically and pathophysiologically, involving various pathogenic mechanisms.[1],[2]

Fragmented QRS complexes (fQRS) are defined as various RSR patterns with or without Q waves on a 12-lead resting electrocardiogram (ECG). It is an electrocardiographic marker of myocardial fibrosis or scar tissue.[3],[4]

In addition, fQRS has been associated with increased sudden cardiac death in patients with idiopathic dilated cardiomyopathy and heart failure.[5],[6]

Cardiac reserve refers to the difference between the rate at which the heart pumps blood and its maximum capacity for pumping blood at any given time. A measurement of the cardiac reserve can be an indicator of a health problem as it can predict the occurrence of heart failure.[7] Coronary angiography remains the clinical gold standard for diagnosis of Coronary artery disease.[8]

We hypothesized that fQRS is an early marker of myocardial involvement in patients with MVA. Therefore, we aimed to investigate the possible relationship between fQRS and myocardial reserve in patients with MVA.


  Patients and Methods Top


The present comparative cross-section study was conducted from August 2018 to September 2019 in the Cardiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. The protocol was approved by our Zagazig University Institutional Review Board which confirmed that all methods were performed in accordance with the relevant guidelines and regulations, and informed consent was obtained from all participants.

Inclusion criteria

Eighty-nine patients with:

  • Typical angina symptoms – Complaints in line with a high probability of coronary artery disease (heavy chest pain or squeezing; a “burning feeling;” or difficulty in breathing, associated with radiation to the left shoulder, neck, or arm, builds in intensity over a period of a few minutes, and begins with exercise or psychological stress), had positive treadmill exercise test and normal coronary angiography.


Exclusion criteria

Patients with:

  • Moderate-to-severe valvular heart disease, a prosthetic heart valve, bundle branches block (left bundle branch block [LBBB]or right BBB), atrial fibrillation, paced rhythm, an atrioventricular block, restrictive, hypertrophic, or dilated cardiomyopathies, congenital heart disease, coronary artery ectasia, a previous history of myocardial infarction, uncontrolled hypertension, hyperthyroidism, hypothyroidism, malignancy, pulmonary, hepatic, renal, and hematological disorders.


Methods

All patients were subjected to the followings:

  • Full history was taken with special emphasis on history of personal, menstrual status and obstetric history, particularly parity
  • The resting baseline 12-lead ECG done with a machine with low-pass filter: 100–150 Hz [Figure 1] and analyzed paying special attention for the detection of electrocardiographic criteria of CSX and whether or not pathological q waves, ST-T-wave changes or recent LBBB
Figure 1: Effects of low-pass filter. Electrocardiogram recording with a low-pass filter of 150 Hz

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The fQRS was defined as the presence of an additional R wave (R2), notching of the R or S wave, or the presence of fragmentation (more than one R2) in two contiguous leads corresponding to a major coronary artery [Figure 2]. There was 99% concordance for the ECG signs of fQRS.
Figure 2: Fragmented QRS in a 64-year-old patient with old myocardial infarction. (a) 12-lead electrocardiogram did not have an abnormal Q wave, (b) multiple R waves were present in III and aVF leads

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  • Treadmill exercise test – Done to all patients according to Bruce protocol and all medications such as beta-blocker and antiarrhythmic agents, was stopped 48 h before the test because these drugs might affect the heart rate (HR) as well as cardiac conduction system. Moreover, all patients of the study had a positive treadmill test. Although ETT had pseudo positive and pseudo negative test with sensitivity of 68% and specificity of 77%.[9] So we did doputamine stress echocardiography (DSE) to all patients to confirm the diagnosis.
  • Laboratory assessment of cardiac enzymes.
  • Echocardiography was performed using aVivid 9 system (GE Healthcare, Little Chalfont, UK) apparatus with harmonic imaging. Baseline echocardiographic variables included end-diastolic and end-systolic diameters, and ventricular volumes, measured with the area-length method and a 4-chamber view. The ejection fraction (EF) was calculated automatically from the volumes obtained by manual tracing of the left ventricular (LV) endocardial border in end-systole and end-diastole. Diastolic function was measured by analyzing: (a) mitral flow: E- and A-wave velocity, E/A ratio, E-wave deceleration time, and isovolumetric relaxation time; (b) pulmonary venous flow: S, D, and A' wave velocity, A' wave duration and S/D ratio; and (c) color M-mode E-wave propagation velocity
  • On completion of the baseline echocardiographic study, the four standard views were obtained in digital format using stress echocardiograph software. Then, dobutamine stress echocardiography (DSE) was performed using a standard protocol.[10] Beta-blocker and calcium-channel blocker were withheld on the morning of the stress tests. Patients fasted for >6 h prior to the tests. After the acquisition of baseline images, intravenous (iv) dobutamine infusion was started at 10 μg/kg/min and increased to 20, 30, and 40 μg/kg/min at 3-min intervals. Atropine was administered iv in 0.5 mg doses, with a maximum dose of 2.0 mg if HR response was inadequate. The infusion was discontinued when the patient reached the target HR of 85% of the age-predicted maximum HR (calculated by subtracting the patient's age in years from 220)


The prespecified infusion end-points were either reaching the maximum dobutamine dose or predicted target HR (0.85× (220-age)). Side-effects requiring cessation of infusion were defined as: (1) arterial hypertension (systolic arterial pressure >220 mm Hg and/or diastolic arterial pressure >120 mm Hg), (2) hypotension (systolic blood pressure <85 mmHg); (3) chest pain; (4) new-onset arrhythmias; or (5) intolerable symptoms experienced by subject. The cardiac reserve was defined as the magnitude of the increased function of the left ventricle. In our study, the global cardiac reserve was assessed by subtracting baseline LV parameters (EF%, cardiac output, and stroke volume) from the peak LV parameters after dobutamine infusion; the maximum percentage that the cardiac output can increase above normal is called the cardiac reserve. Moreover, we calculate the percentage of change (Δ), from baseline to maximum stress: (Δ EF%, Δ COP, and Δ SV) [Table 1].
Table 1: Percentage of changes in cardiac reserve parameters on dobutamine stress echocardiography

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  • Coronary angiography – All patients underwent selective right and left coronary angiography through the right femoral artery. The coronary arteries were imaged in the right and left oblique position using cranial and caudal angulations. The images were recorded digitally at 15 frames/s [Figure 3], and all patients had the absence of any coronary lesions, i.e., nonsignificant lesion < 50% stenosis
  • Exercise ECG – All patients underwent an exercise ECG. The HR, blood pressure, and ECG were recorded at the end of each derivation.
Figure 3: Coronary angiographic images of patients with cardiac syndrome X; Panel (a) left coronary angiography. Panel (b) right coronary angiography

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Statistical analysis

All data were analyzed using SPSS software statistical package for social science version 22 (SPSS, Inc. Chicago, IL, USA). Data were entered checked and analyzed using Epi-Info version 6 and SPP for Windows version 8. Data were summarized using the arithmetic mean, standard deviation, Mann–Whitney U test, validity of screening test, Student's t-test, and Chi-squared test. Multible regression analysis was used for detection of significant predictor of reduced cardiac reserve in MVA patients. Determination of cutoff with associated sensitivity and specificity was performed using Receiver Operating Characteristics (ROC) analysis. Pearson correlation was used to detect the relations between the different study parameters. p value was considered significant if < 0.05


  Results Top


The overall prevalence of patients with fQRS in surface ECG in patients with MVA was 61.8% (55 out of 89 patients).

[Table 2] lists the demographic characteristics of patients with compared with those without fQRS. All demographic data are comparable among both groups except for hypertension (P< 0.05), dyslipidemia (P< 0.02), and hs-C reactive protein (P< 0.03), which were significantly higher in patients with fQRS than in those without fQRS.
Table 2: Demographic characteristics of the study participants

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Echocardiographic and baseline hemodynamic characteristics of patients with compared with those without fQRS are presented in [Table 3]. Clearly, we observe that all parameters were comparable among both groups except for E/e' ratio which was significantly increased (P< 0.05) in patients with fQRS, revealing that patients with fQRS had a higher LV filling pressure than those without fQRS.
Table 3: Resting echo and hemodynamic parameters of the study participants

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Findings of dobutamine stress echocardiographic evaluation of hemodynamic parameters of patients with MVA are summarized in [Table 4]. We found that EF, stroke volume, and cardiac output were significantly lower in patients with fQRS than in those without fQRS; P < 0.001 for all. For the moment, the cardiac reserve was significantly reduced in patients with fQRS than in those without fQRS (P< 0.001) [Table 4].
Table 4: Dobutamine stress echo of study participants

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[Table 1] and [Figure 4] show that the percentage of changes from rest to exercise was significantly lower in patients with fQRS than in those without fQRS, implies that the hemodynamic and cardiac reserve was significantly impaired.
Figure 4: Cardiac reserve was significantly reduced in patients with fragmented QRS than in those without fragmented QRS (P < 0.001)

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Correlation analysis is listed in [Table 5]. Our findings demonstrated that cardiac reserve in patients with CSX was mildly and negatively correlated with systolic blood pressure and with total cholesterol (P< 0.05 in both). Meanwhile, it was considerably correlated with the number of leads with fQRS (P< 0.001).
Table 5: Correlation analysis (r) value between cardiac reserve and clinical, laboratory and echocardiographic parameters in fragmented QRS individuals

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[Figure 5] shows that there was statistically significant negative correlation between number of fQRS complexes and cardiac reserve in study participants.
Figure 5: Significant negative correlation between number of fragmented QRS complexes and cardiac reserve (r = −0.84) and (P <0.001)

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On multiple logistic regression analysis, both, the presence of fQRS and the number of leads with fQRS were the only independent predictors of reduced cardiac reserve in individuals with MVA [Table 6].
Table 6: Independent predictors of reduced cardiac reserve in patients with myocardial infarction with nonobstructive coronary arteries

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Receiver operator charaterisitic curve (ROC) analysis demonstrated that the presence of ≥2 fQRS complexes in ECG was the cutoff value with discriminating sensitivity of 100%, specificity of 92.3% as a predictor of cardiac reserve 3 L in patients with MVA. Area under curve (AUC) was significantly high (0.98) [Figure 6].
Figure 6: Receiver operator characteristics (ROC) curve of fragmented QRS complex as an indicator of cardiac reserve 3 L in microvascular angina (MVA) patients

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  Discussion Top


The current study examined baseline cardiac performance and myocardial reserve in individuals with MVA. More so, we tried to find a relation between fQRS and myocardial reserve in this heterogeneous group of patients. We found that the overall prevalence of fQRS in patients with MVA was 61%. Baseline echocardiography LV mass, dimensions, and systolic function (EF %) were comparable in patients with and with those without fQRS. Patients with fQRS showed a reduced increase in myocardial reserve at dobutamine stress echocardiography in comparison with patients without fQRS, revealing reduced cardiac reserve. The number of leads with fQRS was significantly correlated with the degree of reduced cardiac reserve. The cutoff number of leads with fQRS >2 was the best predictor of reduced cardiac reserve in patients with MVA, with a sensitivity of 100% and specificity of 92.3% and AUC = 0.98.

fQRS develops as a result of heterogeneous electrical activation caused by disrupted ventricular depolarization. It is an electrocardiographic marker of myocardial fibrosis or scar tissue and has been associated with a worse prognosis.[3],[4]

In addition, fQRS has been associated with increased sudden cardiac death in patients with idiopathic dilated cardiomyopathy and heart failure.[5],[6]

Furthermore, the existence of fQRS in patients with known or suspected coronary artery disease leads to a need for revascularization after myocardial infarction and an increase in deaths of cardiac origin.[3],[11]

The use of more sensitive echocardiographic methods may enable the detection of subclinical LV systolic dysfunction and to assess the cardiac reserve in patients with MVA. This is an important task to define the more risky participants in this heterogeneous syndrome, who are on the need for follow-up. This was the main propose of our study.

The present study demonstrated that cardiac reserve in participants with MVA was significantly lower in the group with fQRS on ECG compared with those without fQRS. To the best of our knowledge, this is the first evidence of this relationship.

The overall prevalence of fQRS in our cohort was 63%. This finding supports the presence of a myocardial perfusion dysfunction in the pathophysiology of MVA. In a study conducted by Kaski et al.,[12] transitory myocardial perfusion abnormalities were observed in 25% of patients with MVA. Also with studies on perfusion and LV function using radionuclide agents, results supporting myocardial ischemia have been obtained in 20%–30% of patients with MVA.

In the interim, it has been demonstrated that changes detected in the ECG during chest pain in these patients support the perfusion abnormalities and myocardial ischemia in those patients.

Bugiardini and Bairey Merz[13] found that, in participants with impaired microvascular function, the risk of developing major cardiovascular outcomes was shown to be 2.5%. All these arguments clearly demonstrated the presence of myocardial ischemia in patients with MVA.

With multivariate analysis, the presence of fQRS was found to be a significant independent predictor of reduced cardiac reserve in patients with MVA even after adjustment for cardiovascular risk factors. In this study, we also found that E/e' was significantly increased (diastolic dysfunction) in individuals with fQRS compared with those without fQRS.

Interestingly, we found that ≥2 fQRS complexes in ECG had a sensitivity of 92.3% and accuracy of 94.4% in predicting a cardiac reserve <3 L in MVA.

The lower cardiac reserve in patients with fQRS could be explained by the findings that those patients showing subclinical cardiac dysfunction. This may be related to the presence of abundant myocardial fibrosis, which mostly related to microvascular abnormalities as well as the evident inflammatory predominance. The abnormalities, in turn, disturb both systolic and diastolic cardiac function in individuals with MVA.

Therefore, we can speculate that fQRS is significantly associated with extensive fibrosis and consequently results in cardiac functional abnormalities in this heterogeneous group of patients. As a consequence, we suppose that fQRS is an indicator for decreased cardiac functional reserve in our cohort.

We observed that none of the demographic and biochemical factors were related with the existence of fQRS in our cohort, except hypertension, dyslipidemia, and hs-C reactive protein, which are revealing that the significant impact of the inflammation.

Myocardial remodeling is known to occur gradually in the left ventricle of hypertensive patients, and perivascular hypertrophy and fibrosis started early even without evident LV hypertrophy. Over the years, these changes result in cardiac dysfunction.[14]

The higher incidence of dyslipidemia in patients with fQRS compared with those without fQRS is an interesting observation. The presence of dyslipidemia may increase the inflammatory (as was shown in our study with higher level of hs-CRP in patients with fQRS) and fibrotic burden on the myocardium and consequently the resultant higher incidence of fQRS in patients with MVA.

The main aim of this study was to evaluate the relationship between myocardial and contractile reserve (utilizing dobutamine stress echocardiography) and fQRS in patients with MVA.

Values of stroke volume and ejection fraction were significantly lower in individuals with fQRS than in those without fQRS. Meanwhile, the presence of fQRS was inversely correlated with cardiac output, stroke volume, ejection fraction as well as cardiac reserve. Importantly, the number of fQRS complexes was negatively correlated with cardiac reserve in study participants.

Study limitations

  • Small number of patients
  • How should we follow and treat MVA patients with fQRS? We believe that it is important to do the follow-up data such as the incidence of heart failure hospitalization and ventricular arrhythmias
  • Cardiac scar can be detected magnetic resonance imaging or computed tomography.


Clinical implication

  • We believe that the presence of fQRS in surface ECG provides an important clue for microvascular and contractile dysfunction. In clinical practice, we suppose that earlier detection, through the identification of fQRS in surface ECGs, may help address those issues, prevent adverse outcomes, and improve the quality of life for this heterogeneous group of patients
  • Given its incremental predictive value, improved LV myocardial reserve may have a role in reducing the progress cardiomyopathy and evident heart failure; we supposed that early identification of fQRS as an early marker of subclinical cardiac dysfunction might be of value for risk of patients with MVA
  • For that, it might be a significant predictor for the discovery of subclinical cardiomyopathy in early stages of MVA and can help in the prevention of heart failure development
  • Further follow-up data should be done on a large scale to show how to follow and treat those patients.



  Conclusion Top


In light of our findings, we thought that the existence of fQRS in surface ECG of patients with MVA was correlated with reduced cardiac reserve, and diastolic dysfunction; it has an important clue for microvascular and cardiac contractile dysfunction in these patients. Further follow-up data should be done on large scale to show how to follow and treat those patients.

Financial support and sponsorship

The study was performed at Zagazig University Hospitals with no funding sources.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Das MK, Michael MA, Suradi H, Peng J, Sinha A, Shen C, et al. Usefulness of fragmented QRS on a 12-lead electrocardiogram in acute coronary syndrome for predicting mortality. Am J Cardiol 2009;104:1631-7.  Back to cited text no. 3
    
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Akgul O, Uyarel H, Pusuroglu H, Surgit O, Turen S, Erturk M, et al. Predictive value of a fragmented QRS complex in patients undergoing primary angioplasty for ST elevation myocardial infarction. Ann Noninvasive Electrocardiol 2015;20:263-72.  Back to cited text no. 4
    
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Sha J, Zhang S, Tang M, Chen K, Zhao X, Wang F. Fragmented QRS is associated with all-cause mortality and ventricular arrhythmias in patient with idiopathic dilated cardiomyopathy. Ann Noninvasive Electrocardiol 2011;16:270-5.  Back to cited text no. 5
    
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Pei J, Li N, Gao Y, Wang Z, Li X, Zhang Y, et al. The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure. Europace 2012;14:1180-7.  Back to cited text no. 6
    
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Sniecinski RM, Skubas NJ, London MJ. Testing cardiac reserve: Then and now. 1923. Anesth Analg 2012;115:991-2.  Back to cited text no. 7
    
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Shehata IE, Cheng CI, Sung PH, Ammar AS, El-Sherbiny IA, Ghanem IG. Predictors of myocardial functional recovery following successful reperfusion of acute ST elevation myocardial infarction. Echocardiography 2018;35:1571-8.  Back to cited text no. 8
    
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Gianrossi R, Detrano R, Mulvihill D, Lehmann K, Dubach P, Colombo A, et al. Exercise-induced ST depression in the diagnosis of coronary artery disease. A meta-analysis. Circulation 1989;80:87-98.  Back to cited text no. 9
    
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Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, et al. Stress Echocardiography Expert Consensus Statement-Executive Summary: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur Heart J 2009;30:278-89.  Back to cited text no. 10
    
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Park SJ, On YK, Kim JS, Park SW, Yang JH, Jun TG, et al. Relation of fragmented QRS complex to right ventricular fibrosis detected by late gadolinium enhancement cardiac magnetic resonance in adults with repaired tetralogy of fallot. Am J Cardiol 2012;109:110-5.  Back to cited text no. 11
    
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Kaski JC, Rodriguez-Plaza L, Brown J, Maseri A. Efficacy of carvedilol (BM14, 190), a new beta-blocking drug with vasodilating properties, in exercise-induced ischemia. Am J Cardiol 1985;56:35-40.  Back to cited text no. 12
    
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Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: A changing philosophy. JAMA 2005;293:477-84.  Back to cited text no. 13
    
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Kurdi M, Booz GW. New take on the role of angiotensin II in cardiac hypertrophy and fibrosis. Hypertension 2011;57:1034-8.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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