Clinical Practice Guideline
The Diagnosis of Chronic Coronary Heart Disease
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Background: Chronic coronary heart disease (CHD) and acute myocardial infarction are endemic conditions. In Germany, an estimated 900�000 cardiac catheterizations were performed in the year 2014, and a percutaneous intervention was carried out in 40% of these procedures. It would be desirable to lessen the number of invasive diagnostic procedures while preserving the reliability of diagnosis. In this article, we present the updated recommendations of the German National Care Guideline for Chronic CHD with regard to diagnostic evaluation.
Methods: Updated recommendations for the diagnostic evaluation of chronic CHD were developed on the basis of existing guidelines and a systematic literature review and approved by a formal consensus process.
Results: 8�11% of patients with chest pain who present to a general practitioner and 20�25% of those who present to a cardiologist have chronic CHD. General practitioners should estimate the probability of CHD with the Marburg Heart Score. Specialists can use detailed tables for determining the pre-test probability of CHD; if this lies in the range of 15% to 85%, then non-invasive tests should be primarily used for evaluation and treatment planning. If the pre-test probability is less than 15%, other potential causes should be ruled out first. If it is over 85%, the presence of CHD should be presumed and treatment planning should be initiated. Coronary angiography is needed only if therapeutic implications are expected (revascularization). Psychosocial risk factors for the development and course of CHD and the patient�s quality of life should be regularly assessed as well.
Conclusion: Non-invasive testing and invasive coronary angiography should be used only if their findings are expected to have therapeutic implications. Psychosocial risk factors, the quality of life, and adherence to treatment are important components of these patients� diagnostic evaluation and long-term care.
Chronic coronary heart disease (CHD) and myocardial infarction are widespread diseases (1). In Germany, 361 377 percutaneous coronary interventions (PCIs) were performed in 2014 during in total 906 843 cardiac catheterizations (extrapolated), corresponding to a rate of therapeutic interventions of 40% (2). To reduce the burden on the health system, it is desirable to decrease invasive in favor of non-invasive diagnostic testing without jeopardizing diagnostic and therapeutic safety. Therefore, the current �Diagnosis� chapter of the German National Disease Management Guideline (NVL, Nationale VersorgungsLeitlinie) �Chronic CHD� (3) recommends the use of rational diagnosis algorithms, based on validated clinical and non-invasive methods, prior to initiating invasive diagnostic procedures. In addition, the guideline makes recommendations on the different responsibilities on the primary care level (general practitioner, GP) and on the cardiology level in the differential diagnosis and further work-up of these patients.
The update of the NVL guideline contains several new elements, such as
- the new validated �Marburg Heart Score� to estimate the probability of CHD on the GP level,
- current information about sensitivity and specificity of non-invasive tests,
- updated recommendations on the relevance and significance of exercise ECG testing,
- updated recommendations on the containment of the use of invasive coronary angiography,
- updated recommendations on not using somatic testing in the follow-up of patients with asymptomatic CHD; and
- for the first time recommendations on psychosocial aspects as an essential component of the diagnostic evaluation.
Methods
NVL guidelines are created based on the concepts of the Guidelines International Network (G-I-N), the evaluation criteria for guidelines of the German Medical Association (B�K, Bundes�rztekammer) and the National Association of Statutory Health Insurance Physicians (KBV, Kassen�rztliche Bundesvereinigung) (e1), the guideline rules of the Association of the Scientific Medical Societies in Germany (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) (e2), as well as the German Guideline Appraisal Instrument (DELBI, Deutsches Leitlinienbewertungsinstrument) (e3). The basic methodological approach is described in the general methods report (e4), the specific methodology in the guideline report for the NVL guideline (4). The creation of the 4th edition was organized by the German Agency for Quality in Medicine (�ZQ, �rztliches Zentrum f�r Qualit�t in der Medizin) from 2014 to 2016. The guideline group had a multidisciplinary membership (eBox). Potential conflicts of interest of all parties involved were recorded in a structured fashion according to AWMF specifications and published in the guideline report (4).
Evidence base
For the update, guideline databases were searched for relevant source and reference guidelines. Applicable guidelines with the highest relevance and applicability to the German healthcare situation were selected and appraised using the DELBI instrument (4).
The Medline database (via Pubmed) and the Cochrane database were searched for systematic reviews comparing the use of non-invasive methods with the reference standard, coronary angiography, in patients with (suspected) chronic CHD which were published between January 2007 and May 2014 (eTable 1). The hits identified were appraised in a two-step procedure (eFigure). Included studies were assessed, extracted and graded according to the system of the Scottish Intercollegiate Guidelines Network (e5) (4).
A search for relevant guidelines on the use of invasive coronary angiography in the diagnosis of chronic CHD was performed in February 2015. These guidelines had to be not older than 5 years and published in German or English. The identified guidelines were appraised using the DELBI instrument and a guideline synopsis was created (4).
Pretest probability
Since no method of testing can achieve a sensitivity and specificity of 100%, inaccuracies of the results obtained, both false negative and false positive, are to be expected. Taking into account the probability of the presence of a finding prior to test application (pretest probability) reduces the risk of an inaccurate result and thus increases the chance of a correct result with regard to the detection or exclusion of CHD. The assumptions are based on statistical analyses of data from many controlled studies and take age, sex, risks, symptoms, and test results into account.
Grades of recommendation and consensus-based adoption of recommendations
Grades of recommendation take into account the strength of the underlying evidence, ethical obligations, clinical relevance of the effect measures of the studies, the applicability of the study results to the target patient group, patient preferences, as well as practicability in everyday clinical use and within the structures of the German healthcare system. Two arrow symbols (↑↑) indicate a strong recommendation (�is recommended/indicated�), one arrow symbol (↑) a weak recommendation (�should be considered�), and two arrow symbols directed downwards (↓↓) a negative recommendation (�is not recommended�). The consensus-based adoption of the recommendations was achieved using a Delphi technique and the draft version of the guideline was posted on the publically accessible website www.versorgungsleitlinien.de in November 2015 for comments.
Results
The DEGAM (Deutsche Gesellschaft f�r Allgemein� und Familienmedizin, German College of General Practitioners and Family Physicians) guideline �Chest Pain� was used as a source and reference guideline due to its high methodical quality (DELBI domain 3:0.86) (5). In addition, the ESC guidelines by Montalescot et al., rated lower with regard to methodology, (6) (DELBI domain 3: 0.43), and Perk et al. (7) (DELBI domain 3: 0.43) or their update by Piepoli et al. (8) were taken into consideration.
The diagnostic algorithm in patients with chronic CHD is depicted in the Figure. The basic assumption is that of patients with symptoms (angina pectoris) but no history of CHD who are assessed for potentially underlying obstructive CHD. The diagnostic process in patients with a history of CHD is basically similar.
Differential diagnoses
On the level of GP care, chronic CHD is the cause of the pain in 8�11% of chest pain patients (9�11). Relevant differential diagnoses include chest wall syndrome, psychogenic causes, respiratory tract infections, esophageal conditions, and acute coronary syndrome (9�11). On the level of cardiology care, a cardiac etiology can be assumed in 20�25% of patients with unclear chest pain. The differential diagnosis includes, apart from myocardial infarction, valvular disease (especially aortic valve stenosis), aortic dissection, pulmonary embolism, and inflammatory myocardial and/or pericardial conditions.
History and physical examination
Important aspects of history taking are the exact recording of symptoms (location, development over time, pain quality), the assessment of physical stress tolerance and the identification of risk factors (12). Psychological, somatic and social information are recommended to be collected simultaneously right from the start when the clinical history is taken to prevent early fixation on somatic causes (↑↑, expert consensus).
On the primary care level (GPs), the probability that a patient with chest pain has an underlying obstructive CHD shall be estimated using the Marburg Heart Score (Table 1) ([↑↑] [11, 13] according to [5]). A Marburg Heart Score ≤ 2 points indicates an underlying obstructive CHD with a mean probability of <5%. When interpreting these score results, it is important to take the overall clinical picture into account (statement [11, 13] according to [5]).
On the cardiology care level, the data of the study by Genders et al. (14) are recommended to be used to determine pretest probability; the use of these data is also recommended by the ESC guideline (6) (Table 2) (↑↑, expert consensus based on [6, 14]). The combined presence of the following features defines typical angina pectoris if 3 of the features are present and atypical angina pectoris if 2 are present, while 1 or none of the features defines non-anginal chest pain:
- squeezing pain experienced either retrosternally or in neck, shoulder, jaw or arm
- aggravated by physical exercise or emotional stress
- ameliorated by rest and/or nitroglycerin within 5 minutes ([14] according to [15, 16]).
Basic evaluation
Patients with suspected CHD due to their clinical history and findings are recommended to have a 12-lead resting ECG recorded (↑↑, expert consensus based on [5, 17]). However, systematic reviews have found that the informative value of resting ECGs in patients with stable chest pain or its usefulness to identify stable CHD is generally low (18, 19). Of special importance was the finding that a normal ECG alone does not reliably exclude an underlying CHD. Nevertheless, abnormal Q-waves as a sign of previous myocardial infarction as well as ST-segment and T-wave changes may indicate the presence of CHD (17). This is especially helpful if the patient has no known history of CHD.
In patients with suspected CHD due to their history and findings, resting echocardiography should be considered (↑, expert consensus). Transthoracic echocardiography is a useful tool to assess global and regional myocardial function and can thus contribute to the diagnosis of CHD in patients with regional wall motion abnormalities (hypokinesia, akinesia, dyskinesia) while taking into account the differential diagnosis (6, 20�22).
Non-invasive tests
Exercise ECG is a frequently and widely used diagnostic tool to detect myocardial ischemia as the cause of the corresponding symptoms (12). However, with regard to its diagnostic value in comparison with other testing methods, its lack of diagnostic power for the diagnosis of CHD as the cause of e.g. chest pain is problematic. Assuming a pretest probability of 30�50%, based on clinical history and findings, the posttest probability in case of negative exercise ECG results is between 15 and 30% (own calculations based on Likelihood Ratio [LR] information in Mant et al. [19]). Given a pretest probability of >30%, posttest probability in case of a negative exercise ECG result is on average still higher than 15%; thus, further tests are still required (statement, expert consensus based on [19, 23]). Consequently, a negative finding can only be of help if pretest probability is <30%.
Altogether 31 meta-analyses on the diagnostic value of imaging techniques were identified; of these, the 9 most recent ones with the highest methodological quality were selected for stress echocardiography (e6), myocardial perfusion SPECT (e6�e9), stress-perfusion MRI (e6, e7), dobutamine stress MRI (e10), and CT coronary angiography (e9, e11�e13) to be used as the basis for the recommendations (eTable 2). The results of the various analyses varied considerably. This was primarily due to differences in inclusion criteria, major clinical and methodological heterogeneity of the included primary studies, and rapid advances in the testing techniques.
Sensitivity and specificity considerations
In comparison with invasive coronary angiography, the sensitivity and specificity of most non-invasive techniques to detect obstructive CHD is about 85%. In patients with pretest probabilities of <15% and >85%, the tests have too many false positive or false negative results. This is illustrated by the following example:
In 1000 patients with 15% pretest probability (850 without CHD; 150 with CHD), a diagnostic test with 85% sensitivity and 85% specificity would generate in 850 patients correct results (850 � 0.85 + 150 � 0.85) and in 150 patients (850 � 0.15 + 150 � 0.15) incorrect results. However, if it is directly, i.e. without performing a test, assumed that all patients are healthy, this strategy is correct in 850 patients and incorrect in 150 patients. Thus, it has the same result as the diagnostic test. With decreasing pretest probability, the diagnostic test even performs worse. Only for pretest probabilities >15%, a diagnostic test with the criteria described above generates better results.
For pretest probabilities of 85%, a similar constellation is found. The assumption that all patients have the disease leads to results with an accuracy similar to that of a diagnostic test. If pretest probability increases further, the test performs progressively poorer in comparison with this assumption.
From these considerations it follows that in patients with low pretest probability (<15%) no diagnostic technique should be used to detect obstructive CHD. Instead, another cause of the symptoms should be considered (↑, expert consensus based on [e6�e13]). In patients with high pretest probability (>85%), obstructive CHD should be considered as the cause of the symptoms and treatment planning should be initiated (↑, expert consensus based on [e6�e13]). On patients with moderate pretest probability (15�85%), non-invasive techniques should be used for further work-up to rule out or confirm the suspected obstructive CHD (↑, [e6�e13]).
The non-invasive technique is recommended to be selected according to the pretest probability for obstructive CHD, the suitability of the patient for the respective test, test-related risks, locally available equipment, and local expertise (↑↑, expert consensus). Exercise ECG testing and CT coronary angiography are only recommended for certain pretest probabilities (Figure). Morphological techniques, such as CT coronary angiography, can, in case of a negative result, very reliably rule out CHD; however, these techniques have limitations in the assessment of obstructive versus non-obstructive CHD; thus, they are most helpful if pretest probability is between 15 and 50%. Suitability criteria for the various non-invasive techniques are listed in eTable 3.
In patients with known CHD and clinically suspected disease progression, functional non-invasive imaging techniques should preferentially be used for further work-up (↑, expert consensus). If a previous examination performed with one of these techniques is available, the same technique should be used again, whenever possible, to ensure the findings can be compared (↑, expert consensus).
Invasive coronary angiography
Altogether 9 guidelines making statements with regard to the use of coronary angiography for CHD diagnosis were identified and appraised using the DELBI tool (4). As basis for the recommendations (Table 3), the best rated and most relevant guidelines were used (6, 24, 25). In the context of treatment planning, coronary angiography shall only be offered, if it can be expected that as a result of its findings the patient will undergo a revascularization procedure (Table 3). As detailed in the Revascularization Therapy chapter of the NVL guideline Chronic CHD (3), patients should receive advice based on the patient information brochure �Suspected coronary heart disease: Do I need to undergo cardiac catheterization?�.
Psychosocial evaluation
The aspects discussed in the following are not related to differential diagnosis, but to support a comprehensive biopsychosocial simultaneous diagnosis. Low social status, lack of social support, job-related and family-related stress, depression, anxiety, post-traumatic stress disorder, schizophrenia, bipolar disorder, or certain personality patterns, especially hostility and the so-called Type-D pattern (habitual tendency to experience negative emotions in combination with social inhibition) can have a negative impact on development and course of CHD as well as the quality of life of the patient (7, 8, 26�28). The best prognostic evidence is available for depressive disorder after acute coronary syndrome (29, e14). In addition, treatment options are available for depressed CHD patients which are effective in relieving symptoms of depression (e15). Thus, for the detection of a depressive disorder, a strong recommendation (↑↑, expert consensus based on [e14, e15, 29, 30]), for the detection of other relevant psychological disorders and psychosocial risk constellations a weak recommendation (↑, expert consensus based on [e16-e31, 31�33]) was issued. An overview of suitable medical history questions or questionnaires is provided in eTable 4. In case of positive screening for psychological problems/mental disorder, a clinical diagnosis with explicit exploration of all primary and secondary symptoms according to ICD-10 is recommended to be pursued (↑↑, expert consensus).
Routine follow-up of patients with confirmed obstructive CHD
The GP is responsible for the regular long-term follow-up care of patients with chronic CHD. The corresponding recommendations (Table 4) are based on expert consensus due to the lack of studies evaluating follow-up care.
Apart from a good prognosis, management of chronic CHD aims at achieving a high quality of life for the patient, another key parameter of treatment. For application in clinical practice, an indicative assessment of quality of life using the items of the EuroQoL (EQ-5D) sheet (34) is recommended. The recommendations on quality of life and treatment adherence (Table 4) are based on the ESC guideline (7, 8) and a current position paper of the German Cardiac Society (26).
Acknowledgement
The group of authors would like to thank Dr. Susanne Schorr for the excellent methodological support and coordination during the preparation of the manuscript. We would also like to thank Prof. Dr. Frank Bengel, Prof. Dr. Matthias Gutberlet und Prof. Dr. Christoph Herrmann-Lingen for their very helpful comments on the manuscript.
Conflict of interest statement
Prof. Lindner has received lecture fees from GE Healthcare, Casionpharm and Mediso.
Prof. Albus is receiving honoraria for an authorship related to the topic from Elsevier-Verlag, Deutscher �rzteverlag and Schattauer-Verlag. He has received fees for scientific lectures from Daiichi-Sankyo, WebMD Germany, KelCON GmbH, PCO Tyrol Kongress, and MSD.
Prof. Barkhausen has received lecture fees from Bayer and Philips.
Prof. Silber, Prof. Fleck and Dr. Hasenritter declare no conflict of interest.
Manuscript received on 29 March 2017; revised version accepted on 10 August 2017
Translated from the original German by Ralf Thoene, MD
Corresponding author
Prof. Dr. med. Christian Albus
Klinik und Poliklinik f�r Psychosomatik und Psychotherapie
Universit�tsklinikum K�ln
Kerpener Str. 62
50937 K�ln, Germany
Christian.albus@uk-koeln.de
Supplementary material
eReferences:
www.aerzteblatt-international.de/ref4217
eFigure, eTables, eBox:
www.aerzteblatt-international.de/17m0712
Health Technol Assess 2004; 8: iii1�58 CrossRef
Leitlinien. Methoden-Report 4th edition www.leitlinien.de/mdb/downloads/nvl/methodik/mr-aufl-4-version-1.pdf (last accessed on 26 June 2017).
Department of Radiology and Nuclear Medicine, Schleswig-Holstein University Hospital (UK-SH), Campus L�beck, L�beck, Germany: Prof. Dr. med. Barkhausen
Internal Medicine/Cardiology, German Society of Cardiology (DGK), DGK Capital Office, Berlin, Germany:
Prof. Dr. med. Fleck
Philipps University Marburg, Department of General Medicine, Preventive and Rehabilitative Medicine, Marburg, Germany: Dr. rer. medic. Haasenritter, M. Sc. N., Dipl. Pflegewirt (FH)
Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany: Prof. Dr. med. Lindner
Cardiology Practice, Munich, Germany: Prof. Dr. med. Silber
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