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 Table of Contents  
Year : 2021  |  Volume : 7  |  Issue : 3  |  Page : 202-206

Clinical and angiographic profile of patients with severe left ventricular systolic dysfunction without established coronary artery disease

Department of Cardiology, Gobind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India

Date of Submission27-Jul-2021
Date of Decision12-Nov-2021
Date of Acceptance13-Nov-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Lokesh Khandelwal
F-384, Sarita Vihar, New Delhi - 110 076
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_51_21

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Objective: Coronary artery disease (CAD) is the most common etiology of heart failure with reduced ejection fraction (EF). Coronary angiography is usually not done in patients with severe left ventricular systolic dysfunction (LVSD) without a history of acute coronary syndrome or angina, due to fear of increased risk. Hence, the prevalence of CAD in such cases remains unknown. This study aimed at analyzing the clinical and angiographic profile of the patients with severe LVSD (EF ≤35%) without established CAD. Methods: This was a prospective, observational study conducted from January 2018 to July 2019. One hundred consecutive patients (≥18 years) with severe LVSD (EF ≤35%) without established CAD were assessed for underlying CAD by coronary angiography. Patients were divided into those with no CAD and CAD. Patients having CAD were further classified into those with significant CAD and severe CAD based on angiographic lesion severity. The risk factors contributing to significant CAD were analyzed. Results: Sixty-four patients had no CAD and 36 patients had CAD, of which 34 and 26 patients had significant CAD and severe CAD, respectively. 41.7% patients had double-vessel disease followed by 33.3% and 25% patients having triple-vessel disease and single-vessel disease, respectively. The risk factors for significant CAD were male >55 years/female >65 years, male gender, diabetes mellitus, smoking, and dyslipidemia. Multivariate logistic regression analysis showed diabetes and dyslipidemia to be the independent risk predictors for significant CAD. Conclusion: Occult CAD is present in high proportions in patients with severe LVSD without established CAD specially in presence of risk factors such as diabetes, male >55 years/female >65 years and dyslipidemia. Hence, coronary angiography should be considered strongly in such patients having one or more of these risk factors.

Keywords: Dilated cardiomyopathy, heart failure, ischemic cardiomyopathy, left ventricular systolic dysfunction, occult coronary artery disease

How to cite this article:
Khandelwal L, Trehan VK, Girish M P, Gupta MD, Safal S. Clinical and angiographic profile of patients with severe left ventricular systolic dysfunction without established coronary artery disease. J Pract Cardiovasc Sci 2021;7:202-6

How to cite this URL:
Khandelwal L, Trehan VK, Girish M P, Gupta MD, Safal S. Clinical and angiographic profile of patients with severe left ventricular systolic dysfunction without established coronary artery disease. J Pract Cardiovasc Sci [serial online] 2021 [cited 2023 Mar 23];7:202-6. Available from: https://www.j-pcs.org/text.asp?2021/7/3/202/332491

  Introduction Top

Heart failure (HF) is a major public health problem having high morbidity and mortality and is responsible for significant health expenditures. It has a prevalence of 1%−2% in adults and increases as the population ages.[1] Coronary artery disease (CAD) is underlying etiology in approximately two-thirds of cases of HF with reduced ejection fraction (HFrEF).[2],[3] This etiological differentiation is important as patients with HF due to ischemic origin have a worse prognosis as compared to other etiologies.[4]

Patients with systolic HF are considered to have ischemic etiology when they show angiographic evidence of CAD or history of angina and myocardial infarction (MI). Felker et al.[5] published a definition of ischemic cardiomyopathy (ICMP) for use in clinical research, which considered ischemia as the underlying etiology in patients with obstructive lesions (≥ 75%) in two or more epicardial vessels or left main (LM) coronary artery or the proximal left anterior descending artery (LAD) or having a history of MI or revascularization.

The presence of anginal symptoms or regional wall motion abnormalities on echocardiography is neither specific nor sensitive enough alone to delineate the cause of HF. Myocardial SPECT imaging has only modest value to detect CAD in patients with left ventricular systolic dysfunction (LVSD).[6] Furthermore, in patients with severe LVSD, balanced ischemia due to severe LM or triple vessel disease (TVD) may result in false-negative nuclear perfusion scan due to equal reduction in myocardial perfusion in multiple segments.[7] As an initial approach to look for CAD presence, invasive coronary angiography remains the gold standard test.

Coronary angiography has been given class IIa recommendation by ACC/AHA for management of severe LVSD of unknown cause to identify the presence of significant CAD to guide specific therapies.[8] For patient having symptoms of angina or a history of MI, it is class I indication.[8] According to ESC, it is Class I indication for HF patients having angina, ventricular arrhythmias or aborted cardiac arrest and class IIa for HF patients with intermediate to high pre-test probability of CAD and the presence of ischemia in non-invasive stress tests.[9]

Little is known regarding the prevalence of CAD in patients with severe LVSD without history of MI or angina. Early detection and optimal treatment of patients having underlying CAD, through revascularization procedures and pharmacological treatment with high dose statins and aspirin, can be helpful in preventing adverse ventricular remodeling and improving survival.

  Methods Top

It was a prospective observational study conducted among the patients attending the department of cardiology in our institute after clearance from the Institutional Ethical Committee. Adult patients (≥18 years) with severe LVSD (EF ≤35%) without established CAD were included. Patients with history of angina, history of acute coronary syndrome, and/or coronary revascularization were excluded. Other exclusion criteria were electrocardiography (ECG) evidence of prior MI, congenital heart disease, primary valvular heart disease, NYHA class IV symptoms, acute stroke, severe anemia, active gastrointestinal bleeding, allergy to radiographic contrast, serum creatinine ≥2 mg/dl, and uncorrected hypokalemia.

History of dyspnea (NYHA class), orthopnea, paroxysmal nocturnal dyspnea, angina, fatigue, and palpitations was taken. History of risk factors for CAD including diabetes mellitus, hypertension, dyslipidemia, smoking, and family history of premature CAD was documented. General and cardiovascular examination was done, and associated valvular or congenital heart diseases were ruled out. Standard 12-lead ECG of all cases was documented. EF was assessed by modified. Simpson's method on two-dimensional echocardiography and severity of mitral regurgitation (MR) was documented.

All patients were assessed for underlying CAD (coronary artery stenosis ≥50%)[10] by coronary angiography. SYNTAX score was calculated for those having CAD. Significant CAD was defined as ≥70% coronary artery stenosis. Severe CAD as ≥70% stenosis of LM or proximal LAD or ≥70% stenosis of two or more epicardial vessels.[5]

The sample size for the study was calculated using the following formula: N ≥ (p (1-p))/(ME/Zα)2, where Zα is value of Z at two-sided alpha error of 5%, ME is margin of error and P is prevalence rate. A study by Barik et al.[11] observed that the prevalence of CAD in severe LVSD was 27%. Taking this value as reference, the minimum required sample size with 9% margin of error and 5% level of significance was 94 patients. Calculations: N ≥ (0.27 × (1-0.27))/(0.09/1.96)2 = 93.48 = 94 (approximately). To reduce margin of error, total sample size taken was 100 patients. The comparison was done between significant CAD and no significant CAD groups and factors contributing to significant CAD were analyzed. The continuous variables were presented as mean ± standard deviation and categorical variables as numbers and percentages. The continuous variables were compared using the independent sample t-test and categorical variables using the Chi-square test or Fisher's exact test. Multivariate logistic regression analysis was done to find out the independent predictors of significant CAD. Statistical significance was set at a P < 0.05. Statistical analysis was done using SPSS (Statistical Package for the Social Science) version 17.0 (SPSS Inc., Chicago, IL, USA).

  Results Top

Hundred adult patients with severe LVSD without established CAD were included in the study having a mean age of 54.34 ± 10.89 years. Baseline characteristics of the study population are summarized in [Table 1]. There were 56 male and 44 female patients. Most of the patients (65%) presented with NYHA class II dyspnea. Twenty-two patients were in NYHA class I and 13 patients in class III dyspnea. We excluded patients having class IV dyspnea symptoms. The mean duration of symptoms was 1.6 ± 1.3 years.
Table 1: Baseline characteristics of the patients

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Thirty two patients were diabetics, 41 hypertensives, 17 alcoholics, and 36 smokers with majority of smokers being males. Dyslipidemia was present in 18 patients and family history of premature CAD was present in 17 cases. Sixteen patients were having serum thyroid-stimulating hormone level >5 μIU/ml.

Forty-five percent patients had Left bundle branch block (LBBB) on ECG and LVH was present in 21% cases. Other findings included Right bundle branch block (RBBB), nonspecific intraventricular conduction delay, LAHB. Mean EF of the patients was 28.6 ± 6%. Forty-four percent patients had EF between 21% and 30%. Forty-nine patients had mild, 22 moderate, and 11 severe MR.

CAD was present in 36 patients, of which 34 had significant CAD and 26 had severe CAD. 41.7% (15/36) patients had double vessel disease (DVD), 33.3% (12/36) had TVD and 25% (9/36) had single vessel disease. LAD was the most common vessel diseased in 97.2% (35/36) cases, left circumflex artery in 52.8% (19/36), right coronary artery in 58.3% (21/36) and LM coronary artery in 5 (13.9%) cases. The presence of total occlusion was detected in 41.6% (15/36) cases. Mean Syntax score was 20.93 ± 11.8. 58.3% (21/36) CAD patients had low Syntax score (≤22), 19.4% (7/36) intermediate (23–32) and 22.2% (8/36) high Syntax score (≥33). Angiographic findings of the study population are given in [Table 2].
Table 2: Angiographic findings of the study population

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Predictors that were significantly higher in the patients having significant CAD group included higher mean age (P = 0.02), male gender (P = 0.035), males ≥55 years/females ≥ 65 years (P = 0.002), diabetes mellitus (P < 0.001), smoking (P = 0.01), dyslipidemia (P < 0.001), and lower mean EF (P -0.005).

Characteristics such as hypertension, family history of premature CAD, stages of dyspnea, alcohol intake, hypothyroidism, and presence of LBBB were not found to be significantly different in patients with significant CAD group.

When multivariate logistic regression analysis was done, only diabetes and dyslipidemia were found to be the independent predictors of significant CAD. The result of multivariate regression analysis is shown in [Table 3].
Table 3: Multivariate logistic regression analysis to find out independent predictors of significant coronary artery disease

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Out of 34 patients having significant CAD, elective PCI was done in 15 patients and 8 patients were referred for CABG. Viability testing was done in 6 out of 23 patients undergoing revascularization. Eleven patients did not undergo revascularization and were managed conservatively on medical therapy. There were no deaths and no major peri-procedural complications following coronary angiography.

  Discussion Top

Categorization of patients having LVSD into ischemic and nonischemic causes is of paramount importance. The prevalence of ICMP has been on an increasing trend,[12] and it is currently touted as the most prevalent cause of HF. Hence, virtually, all patients with unexplained HF should be evaluated for the presence of CAD. Individuals with ischemic HF are at elevated risk for adverse cardiac events and death[4] and could potentially be candidates for intervention and secondary preventive measures.

There is a paucity of data on whether patients with an unknown etiology of HF should undergo routine coronary angiography to rule out CAD.[13],[14],[15] The present study was conducted to evaluate the presence of occult CAD in patients with severe LVSD without having a history of angina, previous MI or revascularization. Predominant symptom of these patients was dyspnea and majority of them were being treated on the lines of dilated cardiomyopathy without looking at their coronary anatomy.

About one-third of our patients had underlying significant CAD. In a study by Madabhavi et al.[16] involving 33 patients with severe LVSD, significant CAD was found in 19 (57.6%) patients. Barik et al.[11] demonstrated the prevalence of CAD in 27% of patients with severe LVSD. Hafez et al.[17] involved 145 patients with EF <50% and showed the prevalence of CAD to be 26.2%; however, patients presenting with angina were also included in their study.

The mean age of patients having significant CAD (57.8 years) was higher than those with no significant CAD (52.5 years). Importantly, males ≥55 years/females ≥65 years were a strong predictor of having significant CAD (P = 0.002). The prevalence of significant CAD was significantly higher in males as compared to females. Smokers had a higher prevalence of CAD, and most of smokers were male. Diabetes and dyslipidemia significantly increased the possibility of having significant CAD. Methavigul et al.[18] showed age >60 years, male gender, and diabetes mellitus to be the predictors associated with ICMP. In a retrospective study including patients with severe LVSD presenting with dyspnea, Bayon et al.[19] demonstrated age > 65 years, male gender, smoking, hyperlipidemia, and diabetes mellitus to be associated with increased risk of CAD.

Multivariate logistic regression analysis showed diabetes and dyslipidemia to be independent risk predictors of significant CAD. Our small sample size might affect its results and for better prediction model a larger study is required. Najmy et al.[20] in their study involving patients with HFrEF showed smoking to be independent predictor of CAD.

Thirty of 34 patients with significant CAD had one or more of risk factors including males ≥55 years/females ≥65 years, diabetes, and dyslipidemia. Finding any one of these risk factors had high sensitivity (88.2%) and modest specificity (63.6%) and so it can be utilized regarding decision making on which of these patients should undergo coronary angiography.

Hypertension and family history of premature CAD did not increase the chances of significant CAD. Complete LBBB because of CAD occurs when large area of ischemia is present and more than one coronary artery is affected.[21] In cases of LV systolic dysfunction, complete LBBB is usually a result of myocardial disease rather than CAD. LBBB was not associated with increased chances of having significant occult CAD. Mean EF was significantly lower in patients having significant CAD than those without significant CAD (26.3 ± 5.3 vs. 29.8 ± 6) (P = 0.005), this was in line with a previous study by Whellan et al.[22]

CT coronary angiography requires 50 to 120 ml of contrast for adequate visualization of coronary arteries.[23] Contrast tolerance is a major issue in patients with severe LVSD. The incidence of contrast induced nephropathy can be reduced primarily by minimizing contrast exposure. Invasive coronary angiogram can be done with <15 ml of contrast.[24]

Revascularization offers the potential for improved survival and quality of life, particularly in patients with more extensive multivessel disease and the greatest degree of LVSD and remodeling. STICH trial reported benefit of CABG compared with medical therapy in patients with ICMP, in terms of all-cause mortality, CV mortality, and CV hospitalizations after 10 years of follow-up.[25] Majority of CAD patients in our study had DVD and TVD. Viability testing should be done these patients before revascularization, but because of limiting resources, it was done in 6 out of 23 patients undergoing revascularization. As many patients were having low to intermediate Syntax score, elective PCI was done in 15 patients. Eight patients were referred for CABG. Eleven patients did not undergo revascularization and were managed conservatively on medical therapy as either they refused or their coronary anatomy was not suitable for revascularization.

Coronary angiograms were done by experienced operators using just sufficient amount of non-ionic iso-osmolar contrast, which could delineate coronary anatomy satisfactorily. There was no major intra or postprocedural complication, signifying coronary angiography can be safely done with precautions in patients with severe LVSD having EF as low as 15%. The safety of coronary angiography in patients with EF as low as 20% has been shown previously by Barik et al.[11] There was no mortality from diagnostic angiography, and all the patients were discharged in the stable condition.

It was a single-center study from a tertiary hospital from North India and number of patients included in the study was small. The findings of coronary angiography and echocardiography were not validated by a core laboratory. Patients' information was collected till discharge and follow-up data were not recorded. These were some of the limitations of the study.

  Conclusion Top

There is the presence of occult CAD in high proportions in patients with severe LVSD even when they do not have any other indicator for CAD and significant proportions of these patients have DVD and TVD. Revascularization is possible in many of these cases. Males >55 years/females >65 years, diabetes mellitus, and dyslipidemia were significantly associated with the presence of significant CAD in these patients. Coronary angiography should be considered strongly in such patients having one or more of these risk factors.

Ethics clearance

The institutional ethical committee has approved the study protocol.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Table 1], [Table 2], [Table 3]


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