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ORIGINAL ARTICLE
Year : 2022  |  Volume : 10  |  Issue : 1  |  Page : 14-20

Clinical profile, microbiological spectrum, echocardiographic features, and in-hospital outcomes of patients with definite infective endocarditis: Experience and changes in patterns in two cohort of patients recorded at an interval of 10 years from a tertiary care cardiac center of South India


1 Department of Cardiology, Sri Jaydeva Institute of Medical Sciences, Bengaluru, Karnataka, India
2 Department of Cardiology, GMC, Thiruvananthapuram, Kerala, India
3 Department of Cardiology, Dr. RML IMS, Vibhutikhand, Lucknow, Uttar Pradesh, India

Date of Submission28-Jan-2022
Date of Decision27-Feb-2022
Date of Acceptance03-Mar-2022
Date of Web Publication13-Apr-2022

Correspondence Address:
Dr. Amresh Kumar Singh
Dr. RML IMS, Vibhutikhand, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_7_22

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  Abstract 


Background and Objectives: Infective endocarditis (IE) remains a serious clinical problem with a persistently high morbidity and mortality, despite the availability of improved diagnostic and treatment modalities in the developing world. We examined the microbiological spectrum, clinical profile, echocardiographic features, and in-hospital outcomes of patients with definitive IE.
Materials and Methods: A total of 20 consecutive cases of definitive IE, admitted between March 2017 and August 2018, at a tertiary care cardiac center (Thiruvananthapuram Medical College, India) were included in the study and followed for 6 months. We compared the clinical profile, other features and outcomes of currently enrolled patients (Group-1) with 10 years back (2007) cohort (Group-2) of IE patients (n = 25) at the same institution.
Results: The mean age of the Group-1 was 44.7 (±11.6) years, whereas those in Group-2 were 48.6 ± 12.9. The overall male to female sex ratio was 2.2: 1. The rheumatic heart disease (RHD) was the most common predisposing factor accounting for nearly 40% of all cases in both groups, congenital cardiac lesions accounting for 20% in both groups. The most common significant valve lesion was mitral regurgitation (45% vs. 40% P = 0.032). Fever was the most common complaint at the time of hospital admission in both groups (80% vs. 96%). The most common complication was congestive heart failure in both groups (60% vs. 56%). Blood cultures were positive only in 35% patients from Group-1 to 48% from Group-2 (P < 0.01). The mean vegetation size in Group-1 was 7.6 mm and in Group-2 was 10.8 mm (P = 0.04). Patients with large-sized vegetation had increased incidence of heart failure, and embolic phenomena and mortality. Among Group-1, 5 (25%) patients have undergone surgery compared to Group-2, where only 4 (16%) patients have undergone surgery. The overall in hospital mortality in Group-1 was 5 (25%). Out of them, two patients expired after surgery (surgical mortality 40%). In Group-2, mortality was 7 (28%). Out of them, three patients expired after surgery (surgical mortality 42.8%). The majority (53.3%) of patients were in New York Heart Association Class II at the time of discharge.
Conclusions: The average age of patients presenting with IE in India has increased, while the male predominance is maintained. RHD continues to be the most common predisposing factor. The lower culture positivity rate and lower rates of surgery are worrisome in Indian patients. Despite significant advances in medical technology over the last decade, mortality rate remains the same.

Keywords: Echocardiography, infective endocarditis, rheumatic heart disease


How to cite this article:
Bhole C, Vishwanathan S, Singh AK, Vijay S K. Clinical profile, microbiological spectrum, echocardiographic features, and in-hospital outcomes of patients with definite infective endocarditis: Experience and changes in patterns in two cohort of patients recorded at an interval of 10 years from a tertiary care cardiac center of South India. Heart India 2022;10:14-20

How to cite this URL:
Bhole C, Vishwanathan S, Singh AK, Vijay S K. Clinical profile, microbiological spectrum, echocardiographic features, and in-hospital outcomes of patients with definite infective endocarditis: Experience and changes in patterns in two cohort of patients recorded at an interval of 10 years from a tertiary care cardiac center of South India. Heart India [serial online] 2022 [cited 2023 Jun 2];10:14-20. Available from: https://www.heartindia.net/text.asp?2022/10/1/14/343071




  Introduction Top


Infective endocarditis (IE) is an infectious disease of the endothelial surface of the heart or intra-cardiac devices such as prosthetic heart valves and pacemaker leads. Even in a new era of medical and surgical therapy and interventions, the morbidity and mortality rate is high.[1],[2] The epidemiological, clinical, and microbiological pattern of IE is different in developing countries like India from the western world.

These differences are caused by many factors such as high incidences of rheumatic heart disease (RHD), unrepaired congenital heart disease, irrelevant use of antibiotics, late clinical presentation, and poor outcomes in developing countries.[3],[4] In India, IE is seen in younger patients with RHD and congenital heart diseases. High culture-negative rate is due to improper antibiotic use. The diagnosis of IE is generally late and mortality is high.[5],[6],[7]

We therefore studied the profile and outcome of IE patients presenting to our hospital over 1 year period and compared our results with another cohort of patients admitted to our hospital a decade ago.

Objectives of study

  1. To determine the predisposing conditions for IE
  2. To determine the infective agent in clinically diagnosed IE patients
  3. To assess the two-dimensional echocardiographic findings in clinically diagnosed case of IE
  4. To compare the clinical finding, laboratory parameters, and complications of IE patients with 10-year-old cohort.



  Materials and Methods Top


It was a descriptive single-center study, conducted at medical college Thiruvananthapuram (India) with a retrospective comparison with another cohort of IE patients admitted to our institution a decade ago.

Selection criteria

  1. All patients with clinically diagnosed IE
  2. Age >13 years.


Procedure

All patients with a definitive diagnosis of IE admitted to MCH Thiruvananthapuram between February 2017 and March 2018, were included in this study. The diagnosis of IE was made by Duke criteria. Data were collected by interview method. Detailed clinical examination was done and laboratory investigations were collected. Routine blood tests, Chest X-ray, Echocardiography (ECG), and blood culture of all patients were done. A semi-structured questionnaire was used as tools. Informed consent was taken by patients and the study was approved by institutional ethical committee. The overall cohort was divided into two groups – Group 1 included the all patients admitted Between March 2017 and April 2018 and Group 2 included those admitted between January 2007 and December 2007 (10-year-old cohort). We Compare Group 1 from Group 2. A P < 0.05 was considered to be statistically significant. For all the patients in this study, blood (5–8 ml per bottle) was collected in adult blood culture bottles using standard precautions and processed by a semi-automated blood culture system. The identification of the causative organisms was performed by standard microbiological methods. Transthoracic and/or transesophageal ECG (TEE) were done to find location of vegetation, valve involved, and any cardiac complications. All baseline characteristics, laboratory investigations, treatments given, complications, and outcomes were compared between two groups. Patients were followed up for 6 months after discharge.

Statistical analysis

All statistical analysis was analyzed using SPSS 22.0 version (Manufactured by IBM corporation, Chicago IL, USA.). Data were written as mean ± standard deviation. Group 1 and Group 2 were compared using students paired t-Test. A P < 0.05 was considered statistically significant.


  Results Top


A total of 45 patients were included in this study. Group 1 constituted 20 patients (44.4%) and Group 2 constituted 25 (55.6%) patients. Mostly patients were males with no significant difference in both groups (70% vs. 68%). Sex ratio was 2.21: 1. The mean age in Group 1 was 44.7 (±11.6) years whereas those in Group 2 were 48.6 (±12.9) years. Infective endocarditis was more common in age between 20-60 years in both groups. Of 20 patients in Group 1, 16 (80%) had acute endocarditis, 4 (20%) had subacute endocarditis, as compared to Group 2, 20 (75%) had acute endocarditis, 5 (25%) patients had subacute endocarditis. Infection of native valve was seen in 90% and 88% cases in Group 1 and Group 2, respectively. RHD was the most common predisposing condition in our study (40% vs. 40%) in both groups followed by congenital cardiac lesions (20% vs. 20%) and then degenerative mitral valve disease (15% vs. 16%). Similarly, only three patients (15%) in Group 1 and one patient (4%) in Group 2 had structurally normal heart (P < 0.01). The bicuspid aortic valve was seen in majority of patients in congenital heart disease in both groups (50% vs. 80%; P < 0.01). Other common congenital lesions included in Group 1 were ventricular septal defect in (25%) and ruptured sinus of Valsalva (25%). Fever was the most common symptom at the time of hospitalization in both groups (80% vs. 96%), followed by heart failure which was similar in Group 2 (44%) as compared to Group 1 (40%). Stroke was initial presentation in 3 (15%) patients in Group 1. Among heart failure patients, most of the patients were in New York Heart Association (NYHA) Class III (62.5%, vs. 63%) and Class IV (25% vs. 36%) in Group 1 and 2 respectively at the time of presentation [Table 1]. Among native valve endocarditis patients, mitral regurgitation was most common lesion (45% vs. 40% P = 0.032). Aortic regurgitation was more common in Group 2 (25% vs. 38%, P = < 0.01). Tricuspid regurgitation was seen in three patients in Group 1. The most common complication was congestive heart failure in both groups (60% vs. 56%) (including those having heart failure at the time of admission), followed by hypotension (25% vs. 32%). Stroke was the most common embolic complication seen in 20% in Group 1 and 4% in Group 2 (P < 0.01). 10% patients in Group 1 and 4% of patients in Group 2 had multiple embolic episodes. Mitral valve was mainly involved in both groups followed by aortic valve, 15% patients from Group 1 had tricuspid valve involvement. Vegetation size <10 mm was more common in Group 1 (80%), as compare to Group 2, and Group 2 patients had more number of larger vegetation (44%) (P < 0.01). Mean vegetation size in Group 1 was 7.6 mm and in Group 2 was 10.8 mm (P = 0.04) [Table 2]. Blood culture positivity rate was more in Group 2 (48%), as compare to Group 1 (35%) (P < 0.01) [Figure 1]. Streptococcus viridans were found more common in Group 2 compared to Group 1, (10% vs. 20%; P = < 0.01) and Staphylococcus aureus Scientific Name Search  were seen in 10% in Group 1 and 12% in Group 2 (P = 0.47). In patients with prosthetic valve endocarditis blood culture were negative. Among Group 1 patients, 16 (80%) patients had a history of antibiotic use prior to admission; the most common antibiotic used was amoxicillin with clavulanic acid combination [Table 3].
Figure 1: Comparison of major clinical findings between two groups of infective endocarditis patients

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Table 1: Baseline characteristics

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Table: 2 Echocardiographic features

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Table 3: Blood culture

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All patients received antimicrobial therapy at the time of admission. Antibiotics were given according to the microbial sensitivity reports. In culture-negative cases, antibiotics given according to guidelines. Changing of antibiotics was seen in some patients. In our study, 12 patients (60%) in Group 1 were needed to change antibiotics during hospitalization, 4 (20%) patients were prescribed more than 4 antibiotics and commonly prescribed antibiotics were amoxicillin, gentamicin, piperacillin-tazobactam, and ceftriaxone. In Group 2, overall 13 patients (52%) required a change of antibiotic during initial admission, 4 patients (16%) prescribed >4 antibiotics during hospitalization and commonly prescribed antibiotics were ampicillin, gentamicin, penicillin, and ceftriaxone [Table 4].
Table 4: Treatments

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Among Group 1, 5 (25%) patients have undergone surgery compared to Group 2 where only 4 (16%) patients have undergone surgery. The overall in-hospital mortality in Group 1 was 5 (25%), out of them, 2 patients expired after surgery (surgical mortality 40%). In Group 2 mortality was 7 (28%) (P = 0.04), out of them 3 patients expired after surgery (surgical mortality 42.8%) [Figure 1]. 53.3% of patients in Group 1 were in NYHA Class II at time of discharge among 15 alive cases [Table 5].
Table 5: Mortality

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Follow-up

Out of total discharged patients in Group 1, 53.3% of patients were in NYHA Class II at the time of discharge. Follow-up ECHO was available only in 11 patients, eight patients (72.7%) had calcified nodule over valve, 2 (18.1%) patients were in severe congestive heart failure due to progression of lesion (one severe mitral regurgitation and other severe aortic regurgitation), both of these patients were advised for surgery. One patient expired during follow-up of 1 month, contributing to a total of 30% morality in study [Table 6].
Table 6: Follow up

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  Discussion Top


There are very few prospective comparison studies available regarding changing spectrum of IE from the developing countries like India. Our study was a descriptive study and the aim of this study is to study the profile and outcome of IE in our hospital and to retrospectively compare our results with cohort of patients admitted in the same hospital 10 years back.

The mean age in Group 1 was 44.7 years, whereas those in Group 2 were 48.6 years. However, in western countries, most of the patients were older with a mean age of 56 ± 17 years,[8],[9],[10] but in India, most of the patients have a younger age of presentation between 25 and 40 years.[11],[12],[13] The reason of this difference may be due to the inclusion of pediatric patients in Indian studies and adult patients in western studies. RHD and unrepaired congenital heart disease are prevalent in India which contributes to younger age. Majority of the patients were males in both groups (70% vs. 68%). The sex ratio in the other Indian studies was higher than our study[14] despite RHD commonly affect female patients.

RHD was the most common predisposing condition in this study followed by congenital anomalies and degenerative valvular disease. Congenital anomalies were lower as compared to other Indian studies, which may be because our study excluded pediatric population.[15] The association of RHD was same as in other Indian studies in which RHD found in 42% to 50% of patients. But a study by Madhumitha et al. at Chennai had a relatively lower incidence of RHD which was 17%;[16] however, a study done by Ghosh et al. shows that IE seen in 64% of RHD patients.[17] In our study, Group 2 had more number of bicuspid aortic valve as compared to Group 1 (80% vs. 50% P < 0.01) which is mainly seen in elderly male patients. Degenerative valvular disease-related endocarditis was higher in this study compared to other Indian studies (3.3%–6.7%).[13],[14],[15] A prospective study by Murdoch show that degenerative valve disease was seen in 70% of the native valve endocarditis in western country.[8] This difference may be due to high life expectancy in western. Group 2 had more patients with prosthetic valve endocarditis compared to Group 1 (12% vs. 10%), which is similar to some Indian studies[14],[16],[18] however in a study by Gupta et al. 31.2% cases were of prosthetic valve endocarditis.[19] We know that IE generally does not affect normal valves but in our study Group 1 had a higher number of patients with normal valve as compared to Group 2 (15% vs. 4%, P < 0.01). This finding is similar to a study by Jain et al (10.7%).[14]

Fever was the most common complaint at the time of hospitalization followed by heart failure and stroke in this study. A study by Madhumitha et al., neurological complications seen in 18.3% of IE cases,[16] and 30% of patients in study by Jain et al. had stroke.[14] Among heart failure patients, majority of the cases were in NYHA Class III (62.5%, vs. 63%) followed by Class IV (25% vs. 36%) at the time of presentation. Group 2 had more number of patients with NYHA IV HF. These results are similar to other Indian studies.[18]

Left-sided endocarditis was more common in this study (85%) due to large number of RHD cases which mainly affect left side valves. In native valve endocarditis cases, mitral regurgitation was most common followed by Aortic regurgitation in this study. This may be due to degenerative valve disease mainly involved mitral valve. In Group 1, 15% of patients had right-sided vegetation which presented as tricuspid regurgitation. This was higher than other Indian studies where the involvement of tricuspid valve was seen in 5.8%–8% of cases.[14],[16] Gosh et al. reported 33% of patients with right sides heart involvement and majority had VSD as an underlying predisposing factor.[17]

The most common complication was congestive heart failure in both groups (60% vs. 56%) (including those having heart failure at the time of admission), followed by hypotension (25% vs. 32). This was higher as compared to an Indian study by Garg et al (41.9%).[13] CHF was mainly due to Mitral regurgitation. Renal failure and stroke was more common in Group 1 than Group 2 (25% vs. 32% and 25% vs. 12%) (P < 0.01). Renal failure mainly due to antibiotic toxicity. High incidence of stroke was associated with large vegetation size and prolonged illness.

Culture positivity rate was significantly lower in new cohort compared to 10-year-old cohort (P < 0.01). My finding is similar to other Indian studies in which blood culture positivity rate was 21%–47%.[15],[16],[18],[19] However, a study by Murdoch et al. shows 90% culture positivity rate in western country.[8] These differences may be due to partially antibiotic-treated patients in our study. This may be because 80% of patients from Group 1 had received antibiotics prior to admission, and amoxicillin was the most common antibiotic used. Due to low culture positivity rate in this study, it is very difficult to detect causative agents and to treat them accordingly.

In this study, Streptococcus species and staphylococcus were more common and found in same percentage (10%); however, Streptococcus species was more common in old cohort (P < 0.01). Recently, it was found that staphylococci is the most common causative agent.[8],[10],[11] In some recent Indian studies, it was found that staphylococci was the most common causative agent.[15],[18] Moreover, in some older Indian studies, streptococci is the most common cause of IE.[13],[14],[16] We cannot conclude about the most common causative agent of IE due to low positivity rate.

ECG is the most important imaging modality in diagnosis of IE in culture-negative patients in this study with low positivity rate. In spite of high sensitivity rate of transesophageal ECG, transthoracic ECG (TTE) were done in majority of patients. Less use of TEE was due to high patients load at our center. Vegetation was found in virtually all patients except one patient with VSD. A vegetation size of more than 10 mm was called as large vegetation. Mitral valve was the most common valve involved in both cohort followed by aortic valve involvement. This data was similar to other Indian studies.[13],[16],[17] Group 2 patients had more number of larger vegetation (44% vs. 20%) (P < 0.01). This finding was similar to a study done by Gosh et al., 30%–44% of cases had larger vegetation.[17]

The most common antibiotics used in Group 1 were gentamycin, piperacillin-tazobactam combination, and vancomycin. While the most common antibiotic used in Group 2 was gentamycin, ampicillin, and ceftriaxone. This study shows that more advanced antibiotics were used in new cohort compared to old cohort due to physician's preference and very sick patients in new cohort. Surgery is significantly lifesaving procedure. It is generally needed in 25%–50% of patients.[14] In this study, surgery was done in 25% from Group 1 to 16% from Group 2 patients. This study shows that surgical intervention was increased in recent years. Heart failure and persistent bacterial infection were common indication of surgery. A study by Math et al. where 15% of patients have undergone surgery.[18] The most common surgery was done in both groups was mitral valve replacement.

The overall in-hospital mortality in Group 1 was 25% (surgical mortality 40%) and in Group 2 mortality rate was 28% (surgical mortality 42.8%). The mortality rates were higher than the western countries (12.6%–17.7%).[3],[8],[12] High mortality in this study may be due to the complicated cases and unwillingness for surgery by some patients. Mortality rate in this study was similar to other Indian studies ranging from 4.5% to 29%.[13],[14],[15] Major cause of death in both groups was multi-organ dysfunction (40% vs. 57%; P < 0.01) followed by Refractory heart failure and stroke. This Study shown that the large size vegetations was associated with increased risk of heart failure, embolic phenomenon and mortality.

Study limitations

Our study also had some limitations. Small number of cases were taken in this study. Large number of patients were referred from peripheral hospitals, were very sick and complicated. We excluded pediatric patients of <13 years. We used mainly TTE and less use of TEE which is more sensitive in the detection of small vegetation. Serology testing was not done in culture-negative patients to diagnose fastidious organism.


  Conclusions Top


IE is more common in male. RHD is the most common underlying disease followed by congenital heart disease and degenerative valve diseases. Low culture positivity rate is worrisome and needs to be improved. Large vegetation is associated with a high incidence of heart failure, embolic phenomena, and mortality. Despite significant advances in medical technology over the last one decade, mortality rate of IE remains the same.

Ethical approval

This study was approved by institute ethical committee.

Authors' contributions

  1. Chetan Bhole - Data collection and compilation.
  2. Sunitha Vishwanathan - Idea of this study
  3. Amresh Kumar Singh - Written as manuscript
  4. S.K. Vijay - review of manuscript


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: A population-based study. Lancet 2006;368:1005-11.  Back to cited text no. 1
    
2.
Yacoub MH, Takkenberg JJ. Will heart valve tissue engineering change the world? Nat Clin Pract Cardiovasc Med 2005;2:60-1.  Back to cited text no. 2
    
3.
Tornos P, Iung B, Permanyer-Miralda G, Baron G, Delahaye F, Gohlke-Bärwolf CH, et al. Infective endocarditis in Europe: Lessons from the Euro heart survey. Heart 2005;91:571-5.  Back to cited text no. 3
    
4.
Horstkotte D, Burckhardt D. Prosthetic valve thrombosis. J Heart Valve Dis 1995;4:141-53.  Back to cited text no. 4
    
5.
Gencbay M, Turan F, Degertekin M, Eksi N, Mutlu B, Unalp A. High prevalence of hypercoagulable states in patients with recurrent thrombosis of mechanical heart valves. J Heart Valve Dis 1998;7:601-9.  Back to cited text no. 5
    
6.
Thorburn CW, Morgan JJ, Shanahan MX, Chang VP. Long-term results of tricuspid valve replacement and the problem of prosthetic valve thrombosis. Am J Cardiol 1983;51:1128-32.  Back to cited text no. 6
    
7.
Gohlke-Bärwolf C. Anticoagulation in valvar heart disease: New aspects and management during non-cardiac surgery. Heart 2000;84:567-72.  Back to cited text no. 7
    
8.
Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr., Bayer AS, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: The International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med 2009;169:463-73.  Back to cited text no. 8
    
9.
Moreillon P, Que YA. Infective endocarditis. Lancet 2004;363:139-49.  Back to cited text no. 9
    
10.
Watanakunakorn C, Burkert T. Infective endocarditis at a large community teaching hospital, 1980-1990. A review of 210 episodes. Medicine (Baltimore) 1993;72:90-102.  Back to cited text no. 10
    
11.
Siddiq S, Missri J, Silverman DI. Endocarditis in an urban hospital in the 1990s. Arch Intern Med 1996;156:2454-8.  Back to cited text no. 11
    
12.
Olaison L, Pettersson G. Current best practices and guidelines indications for surgical intervention in infective endocarditis. Infect Dis Clin North Am 2002;16:453-75, xi.  Back to cited text no. 12
    
13.
Garg N, Kandpal B, Garg N, Tewari S, Kapoor A, Goel P, et al. Characteristics of infective endocarditis in a developing country-clinical profile and outcome in 192 Indian patients, 1992-2001. Int J Cardiol 2005;98:253-60.  Back to cited text no. 13
    
14.
Jain SR, Prajapati JS, Phasalkar MA, Roy BH, Jayram AA, Shah SR, et al. Clinical spectrum of infective endocarditis in a tertiary care centre in Western India: A prospective study. Int J Clin Med 2014;5:177-87.  Back to cited text no. 14
    
15.
Choudhury R, Grover A, Varma J, Khattri HN, Anand IS, Bidwai PS, et al. Active infective endocarditis observed in an Indian hospital 1981-1991. Am J Cardiol 1992;70:1453-8.  Back to cited text no. 15
    
16.
Madhumitha R, Ramasubramanian V, Nambi PS, Ramakrishnan B, Gopalakrishnan R, Sathyamurthy I. Profile of infective endocarditis: At a tertiary care referral centre. J Assoc Physicians India 2018;66:60-5.  Back to cited text no. 16
    
17.
Ghosh S, Sahoo R, Nath RK, Duggal N, Gadpayle AK. A study of clinical, microbiological, and echocardiographic profile of patients of infective endocarditis. Int Sch Res Notices 2014;2014:340601.  Back to cited text no. 17
    
18.
Math RS, Sharma G, Kothari SS, Kalaivani M, Saxena A, Kumar AS, et al. Prospective study of infective endocarditis from a developing country. Am Heart J 2011;162:633-8.  Back to cited text no. 18
    
19.
Gupta A, Gupta A, Kaul U, Varma A. Infective endocarditis in an Indian setup: Are we entering the 'modern' era? Indian J Crit Care Med 2013;17:140-7.  Back to cited text no. 19
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