Strontium in atrioventricular conduction disorder: Is it a new target?

Sanjeev S Mukherjee; Dilip Kumar; Debabrata Bera; Arindam Pande; Soumya Patra; Rana Rathore Roy; Rabin Chakraborty

doi:10.4103/jicc.jicc_82_20

ORIGINAL ARTICLE

Year : 2022 | Volume : 12 | Issue : 1 | Page : 25-27

Strontium in atrioventricular conduction disorder: Is it a new target?

Sanjeev S Mukherjee¹, Dilip Kumar¹, Debabrata Bera², Arindam Pande¹, Soumya Patra¹, Rana Rathore Roy¹, Rabin Chakraborty¹
¹ Department of Cardiology, Medica Superspeciality Hospital, Kolkata, West Bengal, India
² Department of Electrophysiology, RTIICS, Kolkata, West Bengal, India

Date of Submission	02-Dec-2020
Date of Decision	02-Dec-2020
Date of Acceptance	19-Dec-2020
Date of Web Publication	08-Feb-2022

Correspondence Address:
Dr. Sanjeev S Mukherjee
Medica Superspeciality Hospital, 127 Mukundapur, E.M. Byepass, Kolkata - 700 099, West Bengal
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jicc.jicc_82_20

Abstract

Introduction: Atrioventricular (AV) block is a common problem worldwide requiring permanent pacemaker implantation, which results in a huge economic burden on society. In our country, the major burden is noted in eastern India. The etiopathological correlation of degenerative conduction tissue disorder does o't explain the differential volume of disease. We speculate environmental link, particularly the influence of elevated trace metals in the pathogenesis of this condition. Purpose: The purpose of the study was to investigate and correlate the concentration of trace metals in blood of patients who have received a permanent pacemaker. Materials and Methods: The blood samples of 81 patients who had permanent pacemaker implantation in the past 3 years were collected and levels of various trace metals were evaluated. It was done using inductively coupled plasma mass spectrometry. The values were expressed in μg/l. Results: There were elevated trace metals in 21 patients and 4 among them had an overlap of more than one abnormal values. Strontium (Sr) surprisingly was elevated in a maximum of 11 patients. The most interesting observation was a trend of Sr being elevated in male sex with AV nodal disease. Conclusion: From this study we hypothesize, Sr affects ion channels in conduction tissue due to its close chemical similarity to calcium. In long run, it could have been inducing fibrosis causing AV blocks. Our observation suggests that trace metal screening may be considered in areas with a high prevalence of AV blocks requiring permanent pacemakers.

Keywords: Atrioventricular block, permanent pacemaker, strontium, trace metals

How to cite this article:
Mukherjee SS, Kumar D, Bera D, Pande A, Patra S, Roy RR, Chakraborty R. Strontium in atrioventricular conduction disorder: Is it a new target?. J Indian coll cardiol 2022;12:25-7

How to cite this URL:
Mukherjee SS, Kumar D, Bera D, Pande A, Patra S, Roy RR, Chakraborty R. Strontium in atrioventricular conduction disorder: Is it a new target?. J Indian coll cardiol [serial online] 2022 [cited 2022 May 27];12:25-7. Available from: https://www.joicc.org/text.asp?2022/12/1/25/337356

Introduction

Atrioventricular (AV) block is the result of disruption of normal electrical conduction from atria to ventricle. Pathological AV blocks are mainly caused by chronic idiopathic fibrosis and sclerosis of the conduction system as seen in Lenegre^[1] and Lev's disease.^[2] Ischemic heart disease is the next major etiology followed by a small contribution from infectious disease and infiltrative cardiomyopathies. Interestingly, the prevalence of this condition in the eastern part of India has been highest compared to the rest of the country. In statistical terms, the incidence is as high as 42% of total pacemaker implants in the country.^[3] There has been an opinion about consumption of mustard oil with high erucic acid causing AV blocks.^[3] However, scientific data for this hypothesis are not robust. In this background, we believed that some environmental and genetic factors could be responsible. Hence, we conducted this study to evaluate other possibilities, like trace metal contamination, causing conduction system injury. AV blocks by trace metal toxicity are known and acute mercury poisoning requiring permanent pacemaker has been reported.^[4]

Materials and Methods

We retrospectively included patients who had a permanent pacemaker implanted from August 2017 to July 2019 in our institute. We collected dietary, occupational, and medication history and took consent for blood sample collection for trace metal screening. The patients continued their routine medications. The trace elements were evaluated using inductively coupled plasma mass spectrometry from a reference laboratory. In this method, liquid samples are first nebulized in the sample introduction system, which generates a fine aerosol that is subsequently transferred to the argon plasma. The high-temperature plasma atomizes and then ionizes the sample, generating ions which are then extracted through the interface region and into a set of electrostatic lenses called the ion optics. The ion optics focuses and guides the ion beam into the quadrupole mass analyzer. The mass analyzer separates ions according to their mass–charge ratio (m/z), and these ions are measured at the detector.^[5] The results were expressed in μg/l. The laboratory reference range was obtained after considering 95% of population as cutoff and that was accepted to maintain standardization.

Results

There were a total of 81 patients who gave consent for blood sample collection and evaluation. Fifty-two (64%) were males and 29 (36%) were females. The mean age of patients was 67.37 ± 9.72 years [Table 1]. Among all, 76 (94%) of participants were ethnic Bengali and 37 (46%) came from Kolkata district. The reason for permanent pacemaker implantation was AV nodal disease in 64 (79%) and 17 (21%) had sinus nodal disease. We screened 21 trace metals but would concentrate on five which showed abnormal values [Table 2]. Abnormal elevated levels were observed in 11 patients with strontium (Sr) (>38 μg/l), 6 patients with arsenic (>5 μg/l), 5 patients with mercury (>5 μg/l), 2 patients each with cadmium (>1.5 μg/l), and cesium (>5 μg/l). Four patients had an elevation of more than one metal in their blood samples. The Sr elevation in AV block compared to Sinus node dysfunction did not achieve statistical significance (P = 0.443), but there was a definite trend [Table 3].

Table 1: Baseline characteristics of the patients (n=81)

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Table 2: Values of different heavy metals (µg/l) in the study population (n=81)

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Table 3: Association between elevated strontium and diagnosis by a cardiologist (n=81)

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Discussion

The main findings from our study were:

Elevated blood Sr levels in patients with pacemaker attracted our attention to an element which has mainly been evaluated for bone pathology
Patients with AV block had a higher chance of abnormal Sr levels, compared to sinus nodal disease
Specific occupational exposure has shown higher Sr levels in this geography. Our study group showing similar trends definitely indicates its association with conduction pathology.

Sr is a fairly reactive chemical occurring as a mixture of four stable (nonradioactive) isotopes, namely 84Sr, 86Sr, 87Sr, and 88Sr, the last of which is the most abundant. It is used in multiple industries such as glass, ceramic, permanent magnets, glazes, and aluminum alloys. The continuous exposure to and inhalation of stable Sr can be lethal to mammalian health, while Sr chromate can cause chromosomal aberrations.^[6] Sr may also interact with secondary cell messengers and transporter systems that normally use calcium. Furthermore, synaptic transmission may be variably affected by Sr, and consequently, at high Sr concentrations, differences in the chemical characteristics of Sr and Ca may prompt neurotoxic and neuromuscular perturbations associated with Sr toxicity.^[6] A study in sheep Purkinje fibers has shown prolongation of action potential due to impairment of inactivation of the slow inward current (Isi). This is due to the dependence of Isi on calcium which has been replaced by Sr. This study also showed that Sr is electrogenic (leading to tails, reduction of the maximum diastolic potential, and masking of the pacemaker potential).^[7] Elevated levels may stem from dietary habits that include the regular intake of Sr-rich grain and fish. Airborne exposure and specific professions like car garage workers as described by Basu et al.^[6] are other reasons for toxic levels. However, Sr per se till now has not been found to have a direct effect on AV blocks. In animal bone studies, it has been shown that high doses of Sr induce growth plate defects (mainly due to the excessive enlargement of the hypertrophic zone) and inhibit calcification, leading to an overproduction of nonmineralized osteoid bone tissue (8). The next place it overloads cell is cardiomyocyte due to replacement of calcium and promoting fibrosis. The endeavor of various government organizations in western countries to reduce Sr levels in drinking water points to its toxic potential.^[8] In our patients with conduction abnormality, its elevated titer raises some serious questions. We need further epidemiological and postmortem studies to establish this association.

Limitations

This is a retrospective analysis and had no control arm. Genetic predisposition cannot be ruled out in absence of genetic analysis which was not part of this study.

Conclusions

From this study, we hypothesize that AV blocks are possible due to Sr toxicity. Our observation suggests that trace metal screening might be considered in areas with a high prevalence of AV blocks requiring permanent pacemaker implantation. Larger randomized trials would be however necessary to establish cause–effect relationship.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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