Published in IJCP April 2021
Clinical Study
Correlation of Paroxysmal and Persistent Cardiac Arrhythmias with Clinical and Echocardiographic Parameters in Patients of Rheumatic Fever and Rheumatic Heart Disease
May 14, 2021 | Sarah Alam, Mu Rabbani, Ms Zaheer, Muhammad Uwais Ashraf, S Hasan Amir
     


Abstract

Introduction: Acute rheumatic fever (ARF) is a multi-system disease caused by an abnormal immunological response after Group A β-hemolytic streptococcus (GABHS) infection. Arrhythmias, atrial fibrillation (AF) occurring in patients of rheumatic heart disease (RHD) are associated with increased risk of stroke. In the Framingham Heart Study, patients with RHD and AF had a 17-fold increased risk of stroke compared with age-matched controls, and the attributable risk was 5 times greater in those with nonrheumatic AF. Material and methods: A total of 92 patients of ARF and RHD from Medicine OPD, Medicine IPD, CCU, Cardiology OPD, Pediatrics OPD, Pediatrics IPD of a tertiary care hospital in North India were recruited in this study. A detailed history, physical examination and routine investigations were carried out. Ambulatory 24-hour Holter recordings were obtained in a standard fashion with 3-channel PC card recorders in all patients. Results: Of the 92 patients studied, 84 had RHD and 8 had rheumatic fever (RF). Maximum number of patients was in the age group 31-40 years. On echocardiography, range of left atrial diameter was 32-81 mm with mean of 50.45 ± 11.27 mm. Thirteen patients were found to have paroxysmal AF detected on Holter monitoring. Thirty-nine patients were found to have pauses detected on Holter monitoring. Out of these, 25 patients were found to have pauses >2.5 seconds. Forty-eight had episodes of paroxysmal supraventricular tachycardia (PSVT) detected on Holter. Seventy-two patients were found to have premature ventricular contractions (PVCs) on ambulatory ECG monitoring. Twenty-five patients had Holter detected episodes of bigeminy; 29 patients had episodes of nonsustained ventricular tachycardia (NSVT) detected on Holter. The association of arrhythmias with age was evaluated. Pauses, PSVT, AF and NSVT were found to have a significant association with advanced age. Severity of mitral stenosis was significantly associated with presence of AF and PVCs. Severity of mitral regurgitation was significantly associated with AF. Eight patients had ARF and all patients were in New York Heart Association (NYHA) Class I. The PR interval was prolonged in 2 patients and was within normal limits in 6 patients. Pauses >1.5 seconds were detected in 2 patients. The duration of the longest pause was 1.60 seconds. Conclusion: RHD is a significant health problem in our region. It commonly affects young patients, compromising the workforce of a country. Only more symptomatic, severe cases belonging to higher functional classes report to hospital. Around one-third of patients are already in AF when they first seek treatment. Even in those patients who are in sinus rhythm, various arrhythmias can be detected on
Holter monitoring.

Keywords: Acute rheumatic fever, arrhythmias, atrial fibrillation, rheumatic heart disease, echocardiography

Acute rheumatic fever (ARF) is a multi-system disease caused by an abnormal immunological response after Group A β-hemolytic streptococcus (GABHS) infection. In 30-50% of cases, recurrent episodes of rheumatic fever (RF) may lead to chronic rheumatic heart disease (RHD), with progressive and permanent damage of the cardiac valves. The associated cardiac morbidity of RF with possible sequelae of heart failure, development of atrial fibrillation (AF), systemic embolism, transient ischemic attacks, strokes, endocarditis, the need for interventions including cardiac surgery and impaired quality-of-life, and shortened life expectancy, impose a heavy burden and has major implications for the individual.

Arrhythmias, AF occurring in patients of RHD are associated with increased risk of stroke. In the Framingham Heart Study, patients with RHD and AF had a 17-fold increased risk of stroke compared with age-matched controls, and the attributable risk was 5 times greater in those with nonrheumatic AF. Holter monitoring is one of the most effective noninvasive clinical tools in the diagnosis and assessment of cardiac symptoms, prognostic assessment or risk stratification of various cardiac populations and in the evaluation of many cardiac therapeutic interventions. Data are limited regarding prevalence of arrhythmias in RHD patients and Holter monitoring is not part of their routine diagnostic work-up. The present work aims to study cardiac arrhythmias by Holter monitoring in patients of RF and RHD.

Material and Methods

This was an open-label, cross-sectional, hospital-based study. A total of 92 patients of ARF and RHD from Medicine OPD, Medicine IPD, CCU, Cardiology OPD, Pediatrics OPD, Pediatrics IPD of a tertiary care hospital in North India were recruited in this study. A detailed history and physical examination were carried out. Investigations carried out included, complete hemogram, blood urea, serum creatinine, urine analysis, liver function test, chest X-ray, electrocardiography (ECG), echocardiography and Doppler study. In patients of RF, additional investigations carried out were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serological examination for streptococcal antibodies (antistreptolysin-O, antideoxyribonuclease B), throat culture or rapid antigen test for Group A streptococcus.

Ambulatory 24-hour Holter recordings were obtained in a standard fashion with 3-channel PC card recorders in all patients. All Holter recorders were subsequently analyzed using specialized software. All results were then visually analyzed to correct for artefact and any erroneous analysis.

Statistical Analysis

All statistical data were analyzed by using SPSS software version 20. Continuous variables were expressed as mean ± standard deviation (SD, Gaussian distribution) or range while proportions were expressed as percentages. Chi-square test was used for comparison of categorical variables between the groups, while unpaired t-test for independent samples was used for comparing continuous variables between two groups. Values of p < 0.05 were considered statistically significant.

Results

Of the 92 patients studied, 84 had RHD and 8 had RF. Maximum number of patients was in the age group 31-40 years. Mean ± SD of age of RHD patients was 34.52 ± 14.47 years (range 13-76 years). Median age was 35 years.

Twenty-eight patients (33.33%) were males and 56 (66.67%) were females. Among the 56 females, 26.8% were seen in 31-40 years age group and around 8% were seen in more than 50 years age group. The most common valvular lesion in RHD patients was mitral stenosis seen in 73 (86.9%) patients, followed by mitral regurgitation seen in 64 (76.2%) patients. Almost equal number of patients had aortic regurgitation and tricuspid regurgitation, which was seen in 25 (29.8%) and 24 (28.6%) patients, respectively. Aortic stenosis was seen in 3 (3.54%) patients. None of the patients had tricuspid stenosis or involvement of pulmonary valve.

On echocardiography, range of left atrial diameter was 32-81 mm with mean of 50.45 ± 11.27 mm. Maximum mitral valve area was 4.40 cm2 and minimum was 0.60 cm2 with mean of 1.41 ± 1.15 cm2. Range of ejection fraction was 18-76% with mean of 58.79 ± 10.44% (Table 1).

Table 1. Echocardiography Findings

 

Minimum

Maximum

Mean

SD

LA diameter (mm)

32.00

81.00

50.45

11.27

MVA (cm2)

0.60

4.40

1.41

1.15

EF (%)

18.00

76.00

58.79

10.44

LA = Left atrial; MVA = Mitral valve area; EF = Ejection fraction.

Figure 1 depicts scatter diagram showing plot of age and left atrial diameter on Echo of RHD patients.

Figure 1. Scatter diagram showing plot of age and left atrial diameter on Echo of RHD patients.

Among the 53 patients who had sinus rhythm on baseline ECG, 13 patients were found to have paroxysmal AF detected on Holter monitoring. Out of 84 RHD patients, 39 patients were found to have pauses detected on Holter monitoring. Out of these 39, 25 patients were found to have pauses >2.5 seconds. Among 39 patients who had pauses detected on Holter monitoring, 26 had chronic AF. Presence of pauses was strongly associated with AF (p < 0.001). Among 13 patients who had pauses and were in sinus rhythm, 2 were found to have paroxysmal AF (Table 2).

Table 2. Presence of Atrial Fibrillation in Relation to Pauses on Holter Monitoring

 

Atrial fibrillation

Total

Present

Absent

Pause

Present

26

13

39

Absent

5

40

45

Total

31

53

84

Out of 84 patients, 48 had episodes of paroxysmal supraventricular tachycardia (PSVT) detected on Holter. Seventy-two patients were found to have premature ventricular contractions (PVCs) on ambulatory ECG monitoring. Twenty-five patients had Holter detected episodes of bigeminy and 29 patients had episodes of nonsustained ventricular tachycardia (NSVT) detected on Holter (Table 3).

Table 3. Arrhythmias Seen in RHD Patients

Arrhythmia

No. of patients, n (%)

Pauses

39 (46.7)

PSVT

48 (57)

AF

31 (37)

Paroxysmal AF

30 (35.7)

PVC

72 (86)

Couplets

52 (62)

Bigeminy

25 (30)

Trigeminy

17 (20)

NSVT

29 (35)

The association of arrhythmias with age was evaluated. Pauses, PSVT, AF and NSVT were found to have a significant association with advanced age. There was an appreciable increase in these arrhythmias after the age of 40 years. Association of arrhythmias with increasing New York Heart Association (NYHA) class was found to be significant for pauses, PSVT, AF, couplets, bigeminy and trigeminy. Severity of mitral stenosis was significantly associated with presence of AF and PVCs. Severity of mitral regurgitation was significantly associated with AF. Severity of tricuspid regurgitation was found to have significant association with presence of bigeminy and NSVT. No association was found between severity of aortic stenosis/aortic regurgitation and cardiac arrhythmias. Arrhythmias significantly associated with left atrial diameter >45 mm were pauses, AF, PVCs, bigeminy, trigeminy and NSVT (Table 4).

Table 4. Association of Arrhythmias with Different Parameters

Parameter

Association

P value

Age

Yes

<0.001

NYHA class

Yes

0.032

Severity of MS

Yes

0.007

Severity of MR

No

0.110

Severity of TR

No

0.06

Severity of AS

No

0.596

Severity of AR

No

0.209

MS = Mitral stenosis; MR = Mitral regurgitation; TR = Tricuspid regurgitation; AS = Aortic stenosis; AR= Aortic regurgitation.

Paroxysmal AF was found to have a statistically significant association with advanced age, higher NYHA functional class and severity of mitral stenosis.

In our study, 8 patients had ARF. All patients were in 11-20 years age group. Mean ± SD of age of RHD patients was 13.25 ± 1.17 years with range of 12-15 years. Out of 8 patients in the RF group, 5 were females and 3 were males. Fever was the commonest clinical manifestation seen, being present in 7 (87.5%) patients. Among the major manifestations, polyarthritis and carditis were the commonest, both being present in 6 (75%) patients. One patient had chorea. None of the patients had erythema marginatum or subcutaneous nodules. Two out of 8 patients gave prior history of sore throat infection 1-5 weeks before disease onset. Six out of 8 patients had mild mitral regurgitation, which was confirmed on echocardiography.

No other valvular involvement was seen. All patients were in NYHA Class I. The PR interval was prolonged in 2 patients and within normal limits in 6 patients. No advanced degree atrioventricular block was observed. None of the patients had junctional rhythm. Two patients had ventricular premature contractions in 24-hour ECG. In none of the patients, ventricular couplets were present and no ventricular runs were detected. Pauses >1.5 seconds were detected in 2 patients. The duration of the longest pause was 1.60 seconds. No patient had AF, PSVT or ventricular tachycardia.

Discussion

Rheumatic heart disease is the world’s most common acquired cardiovascular disease. Worldwide, this disease is the leading cause of heart failure in children and young adults, resulting in disability and premature death and severely affecting the workforce in the developing nations. Because secondary prevention can prevent adverse outcomes, early echocardiography-based identification of silent RHD (showing no clinical signs) with minimal valve lesions by active surveillance programs might be of major importance. In the present study, the commonest valvular lesion among RHD cases was combined mitral stenosis with mitral regurgitation, seen in 22 (26.2%) RHD cases, which was similar to the findings of Joseph et al and Melka A where this pattern was seen in 25.4% cases. However, other studies have reported mitral regurgitation to be the commonest valvular presentation in RHD cases. The differences in the pattern of involvement of valvular lesion could be possibly due to the difference in the age of subjects in various studies.

The mean left atrial diameter in our study was 50.45 ± 11.27 mm which was similar to the findings of Banerjee et al who found it to be 54.25 ± 1.48 mm. In current study, AF was present in 31 (37%) RHD patients on baseline ECG. Other studies have found rates ranging between 5.9% and 40%. Paroxysmal AF was detected on Holter in 13 out of 53 patients who had sinus rhythm on baseline ECG. This finding of 24% in our study was similar to the findings of 27% by Karthikeyan et al and 22.2% by Ramsdale et al.

PVCs occurred in 72 (85.7%) RHD patients, with couplets in 52 (62%) patients, bigeminy in 25 (29.7%) and trigeminy in 17 (20.2%) patients. This was similar to the findings of Ramsdale et al who found PVCs in 87.3% patients in a study done in Liverpool, UK. In our study, pauses were found in 39 (46.7%) patients detected on Holter monitoring. In a study done by Uebis et al to study asystolic pauses in 100 patients having AF by Holter monitoring, pauses longer than 2 seconds occurred in 57% of patients, but longer than 4 seconds only in 6 cases. They also found that a statistically higher frequency was seen in patients with permanent (78.3%) than in those with paroxysmal (24.5%) AF, and in patients with rheumatic valve disease (82.4%) in comparison with the rest (54.3%). They noted asystoles of up to 4 seconds duration in AF can be regarded as “normal” and longer asystoles must be anticipated particularly in patients with rheumatic valvular disease. It is only here that permanent pacemaker therapy appears to be indicated.

Pauses, PSVT, AF and NSVT were found to have a significant association with advanced age and were found to be more common in patients over 40 years of age. Paroxysmal arrhythmias were also found to be more common in advanced age by Ramsdale et al. Significant association of arrhythmias was found with increasing NYHA class for pauses, PSVT, AF, couplets, bigeminy and trigeminy. The possible explanation could be that patients who are having paroxysmal arrhythmias are more symptomatic and thus belong to higher NYHA functional class. Besides, the presence of arrhythmias not only indicates chronicity and severity of lesions but could also be contributing factor for higher NYHA functional class. In our study, subclinical AF detected on Holter was associated with increasing age, higher NYHA functional class and severe mitral stenosis. In our study, presence of PVCs was associated with severity of mitral stenosis. Also, AF was found to be strongly associated with severity of mitral stenosis. Similar findings were noted in earlier studies. Presence of AF was also associated with severity of mitral regurgitation. This may be due to the reason that majority of patients in our study had combined mitral stenosis and mitral regurgitation. A study done by Diker et al noted that the highest frequency of AF in RHD occurs in those with mitral stenosis, mitral regurgitation and tricuspid regurgitation in combination.

In patients of ARF, prior history of sore throat infection 1-5 weeks before disease-onset was found in 2 out of 8 cases and has ranged between 14% and 45.9% among cases in other studies. This wide variation in infection rates could be because of differing immunity status and living conditions among patients in different parts of the world. Cases with sore throat reported at schools and villages should be immediately referred to health centers for confirmation. PR prolongation in many ARF patients has been a well-known finding since 1920.

In the present study, a pause >1.5 seconds on ECG was detected in 2 patients. The duration of the longest pause was 1.60 seconds. In the study by Karacan et al, on standard ECG, the frequency of the first-degree atrioventricular block was found to be 21.9%. ECG at 24 hours detected three additional and separate patients with a long PR interval. Mobitz type 1 block and atypical Wenckebach periodicity were determined in one patient (1.56%) on 24-hour ECG. Lower incidence of conduction abnormalities in our study could be due to small number of cases in our study. However, our results point towards the need of further Holter-based studies in patients of ARF. The prevalence of rhythm and conduction abnormalities may be much higher than determined on standard ECG.

Conclusion

Rheumatic heart disease is a significant health problem in our region. It commonly affects young patients, compromising the workforce of a country. Only more symptomatic, severe cases belonging to higher functional classes report to hospital. Around one-third of patients are already in AF when they first seek treatment. Even in those patients who are in sinus rhythm, various arrhythmias can be detected on Holter monitoring. Detection of paroxysmal AF on Holter can identify high-risk patients in which anticoagulation can be started and may prevent morbidity and mortality from stroke in such patients. Very few cases of RF report to hospital. Rhythm and conduction can be seen in RF patients also, although they are less common as compared to RHD patients. Very few Holter-based studies exist in literature to detect arrhythmias in patients of RHD and RF. Our study provides new insights as such a study has not been conducted previously in our region. More such studies are needed in future, so that high-risk patients can be identified and strategies can be formulated to improve outcomes in such patients.

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