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European Journal of Heart Failure 2007 9(6-7):723-729; doi:10.1016/j.ejheart.2007.02.002
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© 2007 European Society of Cardiology

Clinical diagnosis of left ventricular dilatation and dysfunction in the age of technology

Daniele Rovaia,*, Maria-Aurora Moralesa, Gianluca Di Bellab, Michele De Nesa, Alessandro Pingitorea, Massimo Lombardia and Giuseppe Rossia

a CNR, Clinical Physiology Institute, Via Moruzzi, 1, 56124 Pisa, Italy
b University of Messina, Messina, Italy

* Corresponding author. Tel: +39 050 315 2216; fax: +39 050 315 2166. E-mail address: drovai{at}ifc.cnr.it


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: The diagnostic process has become increasingly dependent on instrumental and laboratory investigation.

Aim: To evaluate the accuracy of symptoms and signs in identifying left ventricular (LV) dilatation and/or systolic dysfunction.

Methods: A group of 100 patients in stable clinical condition and scheduled for cardiac magnetic resonance imaging was prospectively examined by two cardiologists, who were unaware of the individual patient's condition. Patients were interviewed and underwent physical examination.

Results: Several symptoms and signs were associated with LV dilatation and systolic dysfunction at univariate analysis. Using multiple logistic regression, a mitral systolic murmur, a laterally displaced LV impulse, orthopnoea and hepatomegaly were all independent predictors of LV dilatation (end-diastolic volume ≥110 ml/m2) (p<0.0001) and LV dysfunction (ejection fraction <45%) (p<0.0001). The combination of the above variables correctly identified 79% of patients with LV dilatation (sensitivity 51%, specificity 92%), and 82% of patients with LV dysfunction (sensitivity 68%, specificity 90%). Considering LV dilatation and dysfunction, 77% of patients were correctly identified after history alone (kappa=0.13), 84% after LV impulse examination (kappa=0.55) and 86% after cardiac auscultation (kappa=0.58).

Conclusion: Symptoms and signs predict LV dilatation and/or dysfunction with fair sensitivity and excellent specificity.

Key Words: Physical examination • Bedside medicine • Ventricular function • Magnetic resonance imaging

Received October 25, 2006; Revised December 27, 2006; Accepted February 6, 2007


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Recent technological advances have greatly modified the diagnostic process, which is increasingly based on instrumental and laboratory investigations. However, this approach implies a progressive increment in health costs, which could become unbearable for the poorest countries and the economically disadvantaged. In addition, the growing use of technology could distort the physician/patient relationship and multiply the number of inappropriate examinations.

On the other hand, how accurate is clinical diagnosis in light of the methods currently utilized in medicine? To answer this question, we should first survey some information from different specialties. In the Emergency Room, the sensitivity and specificity of physicians recognizing the presence of anaemia, fever and jaundice at physical examination are around 70% [1]. In vascular surgery a correct diagnosis of abdominal aortic aneurysms is made by palpation in 38% of cases; however, in >50% of the remaining patients (in whom the diagnosis emerged after radiological examinations) the aneurysm was actually palpable [2]. The sensitivity of auscultation in detecting a significant stenosis of the common or internal carotid artery is around 55% [3]. In 26% of patients admitted to the Emergency Room, the initial diagnosis is modified by the physical examination performed in the Division of Medicine [4]. In cardiology, the physical variables codified in Killip's classes are independent predictors of prognosis in patients with acute myocardial infarction with or without ST segment elevation [5-7].

The above data suggest that the clinical diagnosis, although underutilized, retains its value; however, its role in cardiology has not been investigated recently. In other, provocatively simplistic terms, should we quit teaching medical students cardiac auscultation and chest palpation, and instead teach echocardiography directly? Or, alternatively, are we spending too much money to obtain information that could be deducted from an accurate patient interview and physical examination? With these considerations in mind, we sought to evaluate the role of the patient interview and physical examination in identifying left ventricular (LV) dilatation and/or systolic dysfunction. Clinical data were compared with the measurements obtained by cardiac magnetic resonance imaging (MRI) [8], one of the gold standards for measuring LV volumes and ejection fraction.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patients
A group of 100 patients scheduled for cardiac MRI was prospectively examined by two experienced clinical cardiologists (DR and M-AM). One cardiologist examined 64 patients and the other, 36 patients. The cardiologists were blinded to the patients condition and the indications for MRI. All patients were in stable clinical condition at the time of the study and all were able to lie down in the MRI scanner for the entire study. Mean age was 59 years (range 18-83 years); 74 patients were male; 46 patients were hospitalised and 54 were outpatients. The final diagnosis was ischaemic heart disease in 55 patients, cardiomyopathy in 10, hypertensive heart disease in 9, valvular heart disease in 6 and congenital heart disease in 4 patients. No cardiac abnormalities were detected in 16 patients.

The investigation conforms with the principles outlined in the Declaration of Helsinki. The study protocol was approved by the Institute's Ethics Committee. Patients were informed of the investigative nature of the study and gave their written informed consent.

2.2. Patient interview and physical examination
Each patient was interviewed by the physician according to a predefined, multiple-answer questionnaire. Patients were asked if they experienced dyspnoea (uncomfortable awareness of breathing) at rest or during physical activity in the past few weeks. According to the New York Heart Association [9], patients were considered to be in functional class I if they experienced no limitation of physical activity; in functional class II if they had a slight limitation, occurring during ordinary physical activity; in class III if they had a marked limitation, occurring during less-than-ordinary physical activity and in NYHA functional class IV if they were severely limited, even at rest. Since enrolled patients had to be able to lie down in the MRI scanner for the duration of the study, none of them was in functional class IV. Patients were also asked if they recently experienced orthopnoea (defined as positioning with ≥2 pillows or in a chair to maintain comfortable breathing during sleep) [10], prior paroxysmal nocturnal dyspnoea (suddenly awakening from sleep with uncomfortable awareness of breathing) [10], nocturnal polyuria (nocturnal micturitions with urinary excretion>during the day) [11], dry cough, weakness (tiredness at rest), fatigue (unusual tiredness on usual activities) and sweating.

In order to explore the reliability of information derived from these referred symptoms, and to minimise bias, no questions about history of previous cardiac or systemic diseases (such as arterial hypertension, diabetes mellitus, myocardial infarction or other) or the diagnosis made by the referring physician, were asked. Similarly, information regarding current and past therapy was not made available to the cardiologists. Following completion of the questionnaire, each patient underwent a general physical examination, including abdominal palpation, inspection and palpation of the chest, chest percussion at the left fifth intercostal space, and auscultation of the heart and lungs. The examined variables were jugular venous distension (defined as a height of the jugular venous waveform ≥3 cm above the sternal angle, with the patient's chest and neck in a 45° position) [12], inferior limb oedema (increased tissue fluid in lower leg or foot after palpation) [10], hepatomegaly (liver edge detectable ≥2 cm below the right costal margin), a sustained LV impulse (increased amplitude of the apical impulse), an enlarged LV impulse (≥3 cm in diameter), a laterally displaced LV impulse (to the left of the mid-clavicular line) by precordial palpation [13] and percussion at the left fifth intercostal space [14], a 3rd heart sound (low-frequency, mid-diastolic sound), a 4th heart sound (low-frequency, late diastolic sound) [10] and a mitral systolic murmur (holosystolic or late systolic murmur, audible at cardiac apex or over left precordium).

2.3. MRI
Cardiac MRI was performed using a 1.5 Tesla whole body scanner (GE Medical Systems, USA). A 4-element cardiac phased-array receiver surface coil was utilized for signal reception. A breath-hold segmented-gradient fast imaging echo, employing steady-state acquisition, triggered with the electrocardiogram, was used to evaluate global LV function according to standard parameters. In each patient a total of 9-12 short-axis views (depending on the LV volumes) and 2 long-axis views (one vertical and one horizontal) were acquired, with a minimum of 30 cine frames for each slice. To measure LV volumes, the endocardial borders were drawn manually in all the short-axis end-diastolic and end-systolic images, end-diastolic and end-systolic LV volumes were calculated using a software program (Mass®, MEDIS, The Netherlands) and LV ejection fraction was derived [15].

2.4. Statistical analysis
Quantitative data were expressed as mean±standard deviation, qualitative data as percentage. The difference in LV volume and ejection fraction between patients with and without the examined symptoms and signs was tested by Analysis of variance (ANOVA) or Welch ANOVA when variances were not equal. The relationship between symptoms, signs derived from general physical examination, LV impulse and cardiac auscultation, and LV volume and ejection fraction at MRI was evaluated by multiple logistic regression. The model construction was done in three steps. In the first step symptoms were considered, in the second step the variables related to general physical examination and LV impulse were added and in the third step cardiac auscultation variables were finally added. At each step, variables were selected by a backward elimination procedure, removing from the model those variables with a p value≥0.10. The performance of each model was evaluated considering the area under the receiver operating characteristics (ROC) curve and its ability to correctly classify patients with or without LV dilatation, with or without LV systolic dysfunction and patients with or without LV dilatation and dysfunction. The ROC curves were based on the probability predicted by the model and were calculated by a non-parametric method. The performance indexes used were sensitivity, specificity, and Kappa concordance index that expresses the proportion agreement beyond chance. A p-value<0.05 was considered to be statistically significant, a p-value between 0.05 and 0.10 was considered as near to significance. All tests were two-tailed. The statistical analysis was made by JMP statistical software, SAS Institute Inc, version 4.0.0.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Symptoms, signs and LV dilatation
Left ventricular end-diastolic volume by MRI was 107±41 ml/m2, ranging from 40 to 215 ml/m2. Several variables were associated with an increase in LV end-diastolic volume at univariate analysis (Table 1). The symptoms significantly associated with LV dilatation were nocturnal polyuria and orthopnea; the signs were a prominent, enlarged or laterally displaced LV impulse, jugular venous distension, a mitral systolic murmur and a third heart sound.


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  		Table 1 Symptoms and signs associated with LV dilatation at univariate analysis

 
A dilatation of LV cavity (end-diastolic volume ≥110 ml/m2) was present in 33 patients. A mitral systolic murmur, hepatomegaly, a laterally displaced LV impulse and orthopnoea were independent predictors of LV dilatation by multiple logistic regression (p<0.0001, Table 2). The combination of these variables was able to correctly identify 79% of patients (kappa=0.48) with a sensitivity of 51%, a specificity of 92% and an area under the ROC curve of 0.77. Shifting the cut-off for LV dilatation to a volume of 125 ml/m2, clinical examination correctly identified 85% of patients (kappa=0.56), with a sensitivity of 56%, a specificity of 95% and an area under the ROC curve of 0.82.


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  		Table 2 Symptoms and signs associated with left ventricular dilatation (end-diastolic volume >110 ml/m2) at multiple logistic regression

 
3.2. Symptoms, signs and LV systolic dysfunction
Left ventricular ejection fraction by MRI was 49±16%, ranging from 13 to 80%. In descending order of power, the symptoms significantly associated with LV systolic dysfunction were orthopnoea, dyspnoea on exertion and nocturnal polyuria. The signs were a prominent, enlarged or laterally displaced LV impulse, hepatomegaly, a mitral systolic murmur, a third heart sound and jugular venous distension (Table 3).


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  		Table 3 Symptoms and signs associated with LV systolic dysfunction at univariate analysis

 
LV systolic dysfunction (ejection fraction <45%) was present in 37 patients. Orthopnoea, hepatomegaly, a laterally displaced LV impulse and a mitral systolic murmur were independent predictors of LV dysfunction at multiple logistic regression (p<0.0001, Table 4). The combination of these variables correctly identified 82% of patients (kappa=0.60) with a sensitivity of 68%, a specificity of 90% and an area under the ROC curve of 0.81. Shifting the cut-off for LV dysfunction to an ejection fraction of 30%, clinical examination correctly identified 86% of the patients (kappa=0.38) with a sensitivity of 37%, a specificity of 95% and an area under the ROC curve of 0.81.


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  		Table 4 Symptoms and signs associated with left ventricular systolic dysfunction (ejection fraction <45%) at multiple logistic regression

 
3.3. Symptoms, signs and LV abnormalities
Left ventricular dilatation and dysfunction were present in 24 patients. Symptoms allowed us to correctly identify 77% of these patients (kappa=0.13). After examination of LV impulse, the percentage of patients correctly identified increased to 84% (kappa=0.55). After cardiac auscultation, the percentage of patients correctly identified increased to 86% (kappa=0.58) (Table 5). Receiver operating characteristics (ROC) curves based on probability predicted after symptoms, after examination of LV impulse and after auscultation are shown in Fig. 1.


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  		Table 5 Accuracy of symptoms, examination of LV impulse and cardiac auscultation in detecting patients with LV dilatation and systolic dysfunction

 


Figure 01
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  		Fig. 1 Receiver operating characteristic (ROC) curves for models of LV dilatation and dysfunction based on symptoms (dotted line), symptoms and examination of LV impulse (dashed line) and symptoms, examination LV impulse and cardiac auscultation (solid line).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The advancement of bio-medical technologies has contributed greatly to the progress of medicine in the past few decades. However, the wide range and availability of technologies has led to a slow, progressive underutilization of the information provided by the patient interview and physical examination. In this study we evaluated whether symptoms and signs still offer reliable information compared to MRI [8], which is one of the most accurate technologies for measuring LV volumes and function. We found that symptoms and signs were able to detect LV dilatation and/or systolic dysfunction with fair sensitivity (between 51 and 68%) and excellent specificity (>90%).

4.1. Importance of nocturnal symptoms
In this study, symptoms occurring at night, such as orthopnoea and nocturnal polyuria, were able to indicate LV dilatation and systolic dysfunction better than symptoms occurring during the day, such as dyspnoea on exertion. This is not very surprising since NYHA functional classification depends upon several factors, including the physician's definition of the patient's ordinary activity and cardiac dysfunction. Furthermore, the reproducibility of NYHA scores has not really been tested [16]. In this respect, orthopnoea is less dependent upon the physician's interpretation, and is associated with a higher rate of hospitalisation and with worsening or no improvement in LV systolic function in patients with heart failure [17].

Nocturnal polyuria was also significantly associated with LV dilatation and dysfunction, this was most likely due to the strict definition criteria used, as frequent nocturnal micturition was only considered as nocturnal polyuria if urinary excretion was greater than during the daytime [11].

4.2. Impact of LV apex examination
Examination of LV impulse contributed greatly to the detection of LV abnormalities. In an earlier study of 100 patients, percussion distance from the mid-sternal line was an independent predictor of the cardiothoracic ratio measured by chest X-radiography [18]. Another previous study of 103 patients reported that a percussion dullness distance of >10.5 cm from the mid-sternal line in the left intercostal space detected an increased LV volume or mass with a sensitivity of 91% and a specificity of 30% with respect to ultrafast computed tomography of the heart [19]. In the same study a diameter of LV impulse >3 cm in the left lateral decubitus detected an increased LV volume or mass with a sensitivity of 100% and a specificity of 40%. In contrast to previous studies, we found a fair sensitivity (62%) but an excellent specificity (91%) of the examination of the LV impulse in detecting LV abnormalities (Table 5).

4.3. Data from cardiac auscultation
A mitral systolic murmur was an independent predictor of LV dilatation and dysfunction. Since only 6% of our patients were affected by valvular heart disease, the reported systolic murmur likely reflected mitral regurgitation due to LV dilatation and mitral annular enlargement. A third heart sound was also significantly associated with LV dilatation and dysfunction. In a previous study of 420 patients with mitral and aortic regurgitation, an audible third heart sound was associated with a lower EF, a greater regurgitant fraction, and restrictive filling [20]. In the 4102 participants from the Studies of Left Ventricular Dysfunction Prevention Trial, the presence of a third heart sound at study enrolment was associated with an increased risk of the composite endpoint of death or development of heart failure [21]. However, the overall inter-observer agreement for detecting S3 was low [22], and the reproducibility was only partly influenced by the physician's experience [23]. Finally, one should remember that the prevalence of a physiological third heart sound in the general population is high (>20%) [24].

4.4. Uniqueness of the approach used
In routine clinical practice, previous disease history is important in the interpretation of current symptoms and signs, and can also impact on report interpretation. In an attempt to avoid such bias, information related to past history and current medications was not made available during the patient interview. Another difference between this investigation and routine clinical practice is that all patients were in a stable clinical condition. In fact, most patients were in a good functional class; very few patients showed lower limb oedema, jugular venous distension or had an audible fourth heart sound. These patient characteristics probably put the investigators in an unfavourable position, since physicians are more accustomed to detecting heart failure than LV abnormalities, and because the clinical features of patients with a low or preserved LV systolic function described in the literature are related to patients with heart failure [25,26].

4.5. Limitations of the study
The patients were examined by two cardiologists and the inter-observer reproducibility was not tested. Additionally, symptoms could have been evaluated more extensively, for example by using a self-assessed functional classification [27], which has recently been shown to independently predict hospitalisation and mortality over 5 years [28]. Nocturnal polyuria was present in only a few patients, which limits the multivariable analysis. Furthermore, the accuracy of several symptoms and signs could be higher if a complete medical history was made available. Finally, the impossibility of studying patients with advanced heart failure (NYHA class IV) by MRI is another limitation of this study.

4.6. Implications for routine clinical practice
Due to increased work load, some physicians are tempted to shorten and simplify the diagnostic process by combining a concise patient interview with the intense utilization of advanced and often expensive technologies, and practically eliminating the physical examination. The high specificity of the clinical approach in detecting LV abnormalities supports the role of bedside medicine in the diagnostic process. In addition, no technology has a cost/effectiveness relationship as favourable as the physical examination. Furthermore, a complete physical examination can unmask abnormalities in different organs and systems that may be the consequence — or the cause — of the heart disease. Finally, physical examination can be easily repeated, even at short time intervals.

4.7. Implications for medical education
The time devoted to sessions aimed at improving physician skills in detecting cardiac abnormalities by patient interview and physical examination at conferences and cardiology courses, is becoming increasingly limited. The same is true for the number of pages devoted to these basic issues in the main cardiology textbooks and to the time dedicated to bedside medicine in academic teaching [29]. Thus, medical students and residents may come to believe that the physical examination in cardiology can be practically replaced by ultrasound procedures and other imaging modalities [30]. There is no doubt that cardiac imaging provides information that vastly exceeds that obtained by patient interview and physical examination [31]; however, it is not always available. Finally, a more clinically-oriented diagnostic process allows better identification of the indications for more complex and expensive tests.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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