Prevalence, clinical characteristics and echocardiographic parameters of arrhythmias among patients with rheumatic heart disease attending Jakaya Kikwete Cardiac Institute: A prospective cohort study

doi:10.21203/rs.3.rs-2075988/v1

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Prevalence, clinical characteristics and echocardiographic parameters of arrhythmias among patients with rheumatic heart disease attending Jakaya Kikwete Cardiac Institute: A prospective cohort study

https://doi.org/10.21203/rs.3.rs-2075988/v1

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Journal Publication

published 17 Aug, 2023

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Background

Arrhythmia is a known complication of rheumatic heart disease (RHD). It is critical to recognize arrhythmias early on so that prompt preventative actions and vigilant monitoring may be considered while treating these patients.

Aim

This study aimed at determining the prevalence, clinical characteristics and echocardiographic parameters of arrhythmias among RHD patients attending Jakaya Kikwete Cardiac Institute (JKCI).

Methodology:

Hospital-based cross-sectional study was conducted among 390 patients with an echocardiography diagnosis of RHD aged 18years and above attending JKCI. Demographic and clinical information was documented. Echocardiography and a resting and 24 hours ambulatory Holter monitoring electrocardiography were done. Chi square test was used to determine association between variables and those with a p value ≤ 0.2 were entered in a multivariate logistic regression analysis to determine the independent factors associated with arrhythmias. P value of < 0.05 was considered statistically significant. The receiver operating curve was used to determine the critical point beyond which arrhythmias develop.

Results

Median age was 39 years IQR (30,52). Females were 257(65.9%). Asymptomatic patients were 208 (53.3%). Most patients belonged to NYHA functional class I&II. The most common valve lesion was mitral stenosis 228 (58.5%). Arrhythmias were found in 276 (70.77%) patients, of which 193 (49.5%) patients were from resting ECG and 83/197 (44.7%) patients from holter electrocardiography. Independent factors for arrhythmias were, New York Heart Association (NYHA) functional class III&IV (a0R 4.67, 95% CI 1.82-12.00 p = < 0.01) and severe left atrial diameter enlargement (aOR 7.28, 95% CI 3.17–16.70 p = < 0.01). The critical point beyond which arrhythmias develop was found to be left atrium diameter > 48mm.

Conclusion

We found a high prevalence of arrhythmias among patients with RHD. The independent predictors of arrhythmias were left atrium dilatation and NYHA functional class III-IV. We recommend close monitoring for arrhythmias among RHD patients in sinus rhythm with higher NYHA functional class and dilated left atrium.

Rheumatic heart disease results from valvular damage secondary to an abnormal autoimmune reaction after infection with group A streptococcal bacteria. This disease has disappeared in developed countries but is still a major problem in the third world countries particularly with low social economic status (1, 2). RHD is a prevalent trigger of arrhythmia, but its frequency and concomitant arrhythmias have been steadily declining in Western countries in recent years. However, in both emerging and third-world nations, the frequency remains high (3).

Study done in India found that out of 84 patients with RHD, AF was present in 31(37%) on baseline ECG. Paroxysmal AF was found in 13 out of 53 patients who had sinus rhythm on baseline ECG. PVCs was present in 72(85.7%), those with couplets where 52(62%). bigeminy was 25(29.7%) and trigeminy 17(20.2), pauses were 39(46.7%) on holter (4). This indicates the importance of close monitoring of these patients and further investigating for arrhythmias by 24-hour holter monitoring even when resting ECG is not suggestive of arrhythmias.

Echocardiography plays a significant role in the evaluation of patients with arrhythmias because it offers information on cardiac function, the arrhythmogenesis, risk stratification, and therapeutic decisions. Arrhythmia pathophysiology in RHD has been linked to structural alterations involving the heart (5).

In a study done on arrhythmias in valvular heart disease, they established a relationship between echocardiographic parameters with arrhythmias, it was found that the critical point beyond which the patient is more prone to get an arrhythmia was when LA diameter > 43 mm, MVA < 1.7cm², mitral MG (mean gradient) > 9mm Hg, LVID D > 50 mm and LVID S > 39 mm. Patients with multivalvular involvement were more prone to arrhythmia (6). In another study AF was associated with LA diameter of greater than 40mm (OR = 7.5, CI 2.4–9.8, p = 0.001). (7). Also, in a cohort study done in Ethiopia AF among RHD patients was associated with LA size of greater than 45mm (8).

Although RHD is still a major problem in developing countries it seems to be a matter of indifference, and little is known about RHD and most of what is known has been derived from studies done thirty years ago. Understanding the pathophysiology of the disease and its sequalae is an important aspect towards management. This study aimed at determining the prevalence, clinical characteristics, and echocardiographic findings of arrhythmias among patients with RHD.

This was hospital-based cross-sectional cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Dar-es-salaam, Tanzania. All patients with Echocardiographic diagnosis of RHD aged 18 years and above were consecutively recruited until a sample size of 390 was reached. The study was conducted from June to December 2021. Cases eligible to participate in the study were included only after being provided with informed consent.

Study procedures

Clinical forms and structured questionnaire were used to obtain the patients demographic and clinical characteristics. Physical examination was done to all patients and all findings were recorded in the clinical forms, patients were classified according to the New York Heart Association (NYHA) based on their symptoms. Electrocardiography was done using A Bionet Cardio 7 machine and reading of the ECG were done manually. Echocardiography was done to all patients using the SC 2000 Siemens ECHO machine. A 24-hour Holter was scheduled and done to all patients who had a normal sinus rhythm on resting ECG using the CONTEC Dynamic ECG Systems Model: TLC9803-CONTEC. Results obtained were recorded in a clinical form.

Data Analysis

Data was entered on SPSS version 23 for statistical analysis. Categorical variables were presented as frequencies and percentages, continuous variables were presented as median and interquartile range (IQR). Chi square test was used to establish the association between social-demographic, clinical characteristics and echo parameters with arrhythmias, all factors with p value < 0.2 were entered into a multivariate logistic regression analysis to determine the independent echocardiographic factors associated with arrhythmias, their adjusted odds ratio (aOR), 95% confidence interval and p-value were determined. P value < 0.05 was considered statistically significant. Receiver operating Curve was used to determine the cutoff point beyond which arrhythmias developed.

Ethical consideration

Ethical clearance to conduct the study was obtained from Muhimbili University of Health and Allied Sciences’ Ethical Review Board. Permission to do the study was obtained from JKCI management. Informed consent was obtained from all study participants before they were enrolled in the study

Socio-demographic and clinical characteristics of the study population

A total of 400 patients with ECHO diagnosis of RHD were recruited during July – December 2021, 7 did not report on their scheduled day for 24-Holter monitoring, 3 denied consent. Median age was 39 years IQR (30,52), majority were female 65.9%, Married were 63.8%, while 51.8% attained primary education. The median BMI was 23kg/m² IQR (14.3, 47.6). 70.5% had no co-morbidities, 72.9% (n = 98) had a mitral valve replacement. We found that 53.3% were asymptomatic for arrhythmias, 58.2% were not on antiarrhythmic medication, most patients were in NYHA class II and III by 40.5% and 30.5% respectively. The commonest valve pathology was mitral stenosis by 58.5% as shown in Table 1.

Table 1

Socio-demographic characteristics of the study participants, n = 390
Variables		n (%)/median (IQR)
Age group (years)
	18–30	101 (25.9)
	31–50	181 (46.4)
	51–60	57 (14.6)
	> 60	51 (13.1)
Median age in years (IQR)		39 (30,52)
Sex
	Male	133 (34.1)
	Female	257 (65.9)
Marital status
	Married	249 (63.8)
	Single	124 (31.8)
	Separated	16 (4.1)
Level of education
	Primary	202 (51.8)
	Secondary school	137 (35.1)
	College / University	51 (13.1)
BMI (kg/m²)
Underweight		28 (7.2)
Normal		225 (57.7)
Overweight		69 (17.7)
Obese		68 (17.4)
Median BMI (in kg/m²)		23 (14.3,47.6)
History of cardiac surgery
Yes		98 (25.1)
No		275 (70.5)
Symptoms of arrhythmias
Symptomatic		182 (46.7)
Asymptomatic		208 (53.3)
NYHA functional class
I		84 (21.5)
II		158 (40.5)
III		119 (30.5)
IV		29 (7.4)
Valve lesion
Mitral stenosis		228 (58.5)
Mitral regurgitation		184 (47.2)
Aortic stenosis		27 (6.9)
Aortic regurgitation		126 (32.3)
Tricuspid regurgitation		187 (47.9)
n: Number of patients, IQR: Interquartile range, BMI: body mass index was calculated using height and weight (BMI = weight in kg /height in meters2), NYHA: New York Heart Association.

The overall prevalence of arrhythmias in this study was 70.77%, of which 49.5% of patients had arrhythmia on ECG and out of 197 patients who did holter 88 (44.7%) had paroxysmal arrhythmias. The most common arrhythmia on ECG was atrial fibrillation by 57%, whereas the most common arrhythmias on holter ECG was ventricular ectopic by 40.5%. Other arrhythmias in order of importance included atrial flutter, supraventricular ectopic, paroxysmal AF, Junctional rhythm, sinus arrhythmias, non-sustained ventricular tachycardia and paroxysmal atrial flutter. (Fig. 1)

Socio-demographic and clinical characteristics associated with arrhythmias

Among patients with RHD, arrhythmias occurred more common in age > 60 (88.2%) and was more in males (74.4%). High proportion of patient with arrhythmias had comorbidities (76.5%), symptoms of arrhythmias (80.8%), NHYA III-IV functional class (91.9%), Tricuspid regurgitation (83.4%) and had no history of cardiac surgery (70.9%). Factors that were significantly associated with arrhythmias were age, presence of symptoms of arrhythmias, higher NYHA class, use of anti-arrhythmic medication, mitral stenosis, and tricuspid regurgitation as shown in Table 2.

Table 2

Social demographic and clinical characteristics associated with the development of arrhythmias n = 390
				Presence of arrhythmia
Variables				Yes (%)	No (%)	P - value
Age (years)
	18–30			69 (68.3)	32 (31.7)	0.014
	31–50			119 (65.7)	62 (34.3)
	51–60			43 (75.4)	14 (24.6)
	> 60			45 (88.2)	6 (11.8)
Sex
	Male			99 (74.4)	34 (25.6)	0.252
	Female			177 (68.9)	80 (31.1)
Comorbidities
	Yes			13 (76.5)	4 (23.5)	0.787
	No			263 (70.5)	110 (29.5)
Cardiac surgery
		Yes		69 (70.4)	29 (29.6)	0.928
		No		207 (70.9)	85 (29.1)
Symptoms of arrhythmias
		Symptomatic		147 (80.8)	35 (19.2)	< 0.001
		Asymptomatic		129 (62.0)	79 (38.0)
NYHA Functional Class
			NYHA I-II	140 (57.9)	102 (42.1)	< 0.001
			NYHA III-IV	136 (91.9)	12 (8.1)
Valve lesion
			Mitral stenosis	177 (77.6)	51 (22.4)	< 0.001
			Mitral regurgitation	135 (73.4)	49 (26.6)	0.286
			Aortic regurgitation	88 (69.8)	38 (30.2)	0.739
			Tricuspid regurgitation	156 (83.4)	31 (16.6)	< 0.001

4.5 Echocardiographic parameters associated with arrhythmias

Patients with arrhythmias as displayed in Table 3 had a decreased TAPSE (85%), severe left ventricular dysfunction (95%), evidence of pulmonary hypertension (82.4%), pericardial effusion (78.1%), moderate decreased MVA (86.5%) and severe increased mean gradient (80.2%). Left ventricular dysfunction (p = 0.004) and evidence of pulmonary hypertension (p < 0.001) was significantly associated with arrythmias. Arrhythmias was more common among patients with severely dilated LA (82.5%), moderate dilated LVIDd (75%) and mild dilated LVIDs (80%). LA diameter was the only factor significantly associated with arrhythmias p < 0.001.

Table 3

Echocardiographic characteristics associated with arrhythmias n = 390
		Presence of Arrhythmia
Variable		Yes (%)	No (%)	P-value
TAPSE
	Normal	208 (67.1)	102 (32.9)	0.002
	Decreased	68 (85)	12 (15)	0.002
LVEF median (IQR) = 57.13(46.33,57.13)
	Normal	154 (65)	83 (35)	0.004
	Mild dysfunction	73 (75.3)	24 (24.7)
	Moderate dysfunction	30 (83.3)	6 (16.7)
	Severe dysfunction	19 (95)	1 (5)
Evidence of Pulmonary Hypertension
	Yes	131 (82.4)	28 (17.6)	< 0.001
	No	145 (62.8)	86 (37.2)	< 0.001
Pericardial effusion
	yes	25 (78.1)	7 (21.9)	0.340
	no	251 (70.1)	107 (29.9)	0.340
Presence of thrombus
	Yes	7 (58.3)	5 (41.7)	0.344
	No	269 (71.2)	109 (28.8)	0.344
Mitral Valve area median (IQR) = 1.79(0.83,4.5)
	Mild decreased	45 (70.3)	19 (29.7)
	Moderate decreased	32 (86.5)	5 (13.5)
	Severe decreased	104 (80.6)	25 (19.4)	0.116
Mean gradient median (IQR) = 7.8(5,7.8)
	Mild increased	4 (80)	1 (20)
	Moderate increased	43 (74.1)	15 (25.9)
	Severe increased	134 (80.2)	33 (19.8)	0.572
LA diameter mean (IQR) = 52.25 (45,59)
	Normal	13 (25.5)	38 (74.5)	< 0.001
	Mild dilated	23 (60.5)	15 (39.5)
	Moderate dilated	33 (66)	17 (34)
	Severe dilated	207 (82.5)	44 (17.5)
LVIDd mean (IQR) = 46.3(41.25,55.7)
Normal		76 (73.8)	27 (26.2)	0.658
Mild dilated		2 (50)	2 (50)
Moderate dilated		6 (75)	25 (2)
Severe dilated		192 (69.8)	83 (30.2)
LVIDs mean (IQR) = 31.6(27.06,42.2)
	Normal	171 (66.5)	86 (33.5)	0.681
	Mild dilated	28 (80)	7 (20)
	Moderate dilated	8 (72.7)	3 (27.3)
	Severe dilated	69 (79.3)	18 (20.7)

Independent factors associated with arrhythmias

Logistic regression analysis using multivariate model (Table 4) with eight factors from chi-square table. When the eight characteristics were adjusted for confounders two factors were found to be independently associated with arrhythmias, NYHA III &IV (aOR 4.67 95% CI 1.82-12.00) p < 0.001) and severe LA enlargement (aOR 7.28 95% CI 3.17–16.70) p < 0.01).

Table 4

Logistic regression analysis showing independent factors associated with arrhythmia
		Univariate analysis			Multivariate analysis
Variable		cOR	95% CI	P-value	aOR	95% CI	P-value
Age groups(years)
	18–30	1.12	0.67–1.89	0.661	0.93	0.49–1.79	0.845
	51–60	1.60	0.81–3.15	0.173	0.90	0.40–2.03	0.800
	> 61	3.91	1.58–9.66	0.003	2.18	0.76–6.21	0.145
	31–50	Ref
Symptoms
	symptomatic	1.63	1.23–2.16	< 0.001	1.44	0.81–2.57	0.212
	asymptomatic	Ref
NYHA class
	III & IV	8.26	4.34–15.71	< 0.001	4.67	1.82–12.00	0.001
	I & II	Ref
Mitral stenosis
	yes	2.21	1.42–3.44	< 0.001	1.106	0.59–2.06	0.750
	no	Ref
Tricuspid regurgitation
	yes	3.44	2.13–5.54	< 0.001	1.61	0.77–3.36	0.203
	no	Ref
Pulmonary hypertension
	yes	2.77	1.70–4.52	< 0.001	0.90	0.43–1.90	0.789
	no	Ref
Left atrial diameter
	mild enlarged	4.48	1.81–11.08	< 0.001	3.45	1.25–9.49	0.017
	moderate enlarged	5.67	2.40–13.40	< 0.001	3.23	1.20–8.69	0.021
	severe enlarged	13.75	6.77–27.94	< 0.001	7.28	3.17–16.70	< 0.001
	normal	Ref
Left ventricular ejection fraction
	mild dysfunction	4.48	1.81–11.08	0.001	0.95	0.49–1.84	0.875
	moderate dysfunction	5.67	2.40–13.40	< 0.001	1.59	0.46–5.49	0.464
	Severe dysfunction	13.75	6.77–27.94	< 0.001	2.73	0.32–23.56	0.361
Key: cOR: crude Odds Ratio, aOR adjusted Odds Ratio, Ref: Reference category,

The cut off point for left atrial dilatation beyond which arrhythmias develop in our study as shown in Fig. 2 was found to be 48mm with a sensitivity of 81.88% and positive predictive value of 84.64%.

Arrhythmias are common in RHD patients at JKCI, according to this study. Arrhythmias were identified in 276/390 (70.77%) of patients, with 193/390 (49.5%) having arrhythmias on the resting ECG. A 24 hours holter was performed on 197/390 (50.5%) of the patients, and it was discovered that 88/197 (44.7%) of them experienced arrhythmias. This is in contrast with a study done by Behra S et al found that out of 268 patients with RHD 45.5% had arrhythmias (6). Another study by Pourafkari L et al on factors associated with arrhythmias in rheumatic mitral stenosis, they found that arrhythmias was present in 33% of patients however in this study they only assessed for atrial fibrillation (9).

In a meta-analysis done globally among 75,637 patients with RHD it was found that 32.8% patients had arrhythmias, however this study did not assess for paroxysmal arrhythmias (10).

Bouleti C et al found the prevalence to be 38%, however this study only involved patients who had undergone percutaneous mitral valve repair (11). The Soweto Heart Study found the prevalence of arrhythmias to be 46.8% (8).

Types of arrhythmias in this study were AF (57%), atrial flutter (15.5%), PAC (8.8%), junctional rhythm (7.8%), sinus arrhythmia (7.3), PVC (3.1%) and multifocal atrial tachycardia (0.5%). Similarly, Behra S et al found that AF was present in 37.2% of patients followed by ventricular ectopic beats in 8.9% patients, multifocal atrial tachycardia in 1.8% patients. (6) Holter monitoring in patients with mitral stenosis and sinus rhythm in a study done by Ramsdale DR et al showed that supraventricular ectopic was in 93.6% patients, paroxysmal atrial fibrillation was present in 22.2% patients, atrial flutter was in 7.9% patients, ventricular ectopic was in 87.3% and 1 patient had non sustained supraventricular tachycardia. Overall, our findings and findings from previous studies suggest that supraventricular arrythmias are the most common arrhythmias in RHD. The variation in prevalence and types of arrhythmias is due to the use of different definitions when diagnosing arrhythmias, and the device used to detect arrhythmias.

This study found that increase NYHA functional class was significantly associated with arrhythmias in both univariate and multivariate analysis. Higher NYHA functional class occurs in patients with severe valve disease and chamber dilatation which is the cornerstone for arrhythmias. Alam et al found that association of arrhythmias with increasing NYHA class was significant for pauses, paroxysmal supraventricular tachycardia, AF, couplets, bigeminy and trigeminy (4)

In this study we found that mitral stenosis, tricuspid regurgitation, left ventricular dysfunction, pulmonary hypertension, and LA diameter were significantly associated with arrhythmias in univariate analysis. However, in multivariate analysis, only LA dilatation was significantly associated with arrythmias. This observation is similar to that of Diker E et al (12). In contrast, a Meta-analysis of correlates of AF in RHD by Noubiap et al found that mitral valve disease and tricuspid valve involvement (OR:4 95% CI 3.0-5.3) and LA dilatation (MD:8.1mm 95% CI 5.5–10.7) was associated with AF (10). The observed difference could be due to different methodology, study population and sample size.

In a study done in India on VHD they found that LVIDd and LVIDs was significantly associated with arrhythmias however, this finding was only for mitral regurgitation, aortic regurgitation and aortic stenosis lesions, when the parameters where compared to multivalvular involvement it appeared not to be significantly associated with arrhythmias (6). Diker E et al found that LVIDd and LVIDs were not statically significant associated with arrhythmias, this finding is similar to the finding in our study.

In receiver operating curve we found that the critical point beyond which arrhythmias develop was LA diameter > 48mm. This is not similar to that of S Behra et al, they found that the critical point for LA dilatation of > 43mm. This could be due different ethnicity among the two studies.

In our study mitral valve area and mean gradient was not significantly associated with arrhythmias this contrasts with S Behra et al, they found that mitral valve area and mean gradient to be significant associated with arrhythmias in univariate model, however in their multivariate analysis it was not significant. Our finding was like that of Diker E et al., MVA did not show any correlation as a predictor for AF.

The recentness of this study is that no current data is available in Tanzania that characterizes arrhythmias among RHD patients, this study shows that LA dilatation is a good predictor of arrhythmias and thus can be used in risk stratification among these patients. Holter ECG has shown to be an important tool in detecting arrhythmias among patients with normal sinus rhythm in resting ECG.

RHD: rheumatic heart disease; ECG: electrocardiography; JKCI: Jakaya Kikwete Cardiac Institute; NYHA: New York Heart ECHO: echocardiography; LA: left atrium;

Ethics approval and consent to participate

All participants provided written informed consent before enrollment in the study. The study was approved by the local ethics committee of Muhimbili University of Health and Allied Sciences’ Ethical Review Board. Permission to do the study was obtained from Jakaya Kikwete Cardiac Institute management. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable

Availability of data

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request and materials.

Competing interests

The authors declare no competing interests.

Authors’ contributions

CDM, RM: conceptualized, data collection, data analysis, drafted the initial manuscript

PP: Data analysis and interpretation

EK, AB: data collection, critical review of the manuscript

All authors critically reviewed the manuscript and agreed on the final version.

Funding

Self-funded

Acknowledgements

The authors would like to thank all the institutions, health staff and study participants involved in the study.

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No competing interests reported.

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You are reading this latest preprint version

Prevalence, clinical characteristics and echocardiographic parameters of arrhythmias among patients with rheumatic heart disease attending Jakaya Kikwete Cardiac Institute: A prospective cohort study

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Journal Publication

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Abstract

Background

Aim

Methodology:

Results

Conclusion

Figures

Background

Methods

Study procedures

Data Analysis

Ethical consideration

Results

Socio-demographic and clinical characteristics of the study population

Socio-demographic and clinical characteristics associated with arrhythmias

4.5 Echocardiographic parameters associated with arrhythmias

Discussion

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1