Ischemia Reversal Therapy as an add-on Therapy for Ischemic Heart Disease: A Pilot Study based on SPECT Myocardial Perfusion Imaging

Rohit S¹, Jagdish H², Chandrakant C², Sujit N³ and Rahul M^4*
*Correspondence: Rahul M, Department of Research and Development, Madhavbaug Cardiac Care Hospital, Raigad, Maharashtra, India, Tel: +919821014716, Email:

Keywords

Ischemia reversal therapy; SPECT-MPI; VO₂ peak

Introduction

The Registrar General of India reported that IHD led to 17% of total deaths in 2001-2003, which increased to approximately 42% of total deaths in 2013 [1]. There is an urgent need for developing preventive measures and various treatments for management of the disease state in stable IHD patients.

It thereby becomes important to acknowledge the need for better diagnostic and/or prognostic modalities to direct the best of therapy to individual patients. Single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is known to top the list of non-invasive diagnostic tools that help to assess myocardial ischemia from obstructive coronary artery disease. The results also aid in directing correct type of therapy and may also predict which patient may respond to the chosen therapy [2-4]. The combination of allopathic treatment and traditional Indian medicine, i.e., Ayurveda is a promising approach for the treatment of IHD. However, there is a paucity of evidence-based studies related to Ayurveda in combination with allopathic medicine in the treatment of stable IHD patients. Ischemia reversal program (IRP) is one such treatment modality designed to on the basis of Ayurvedic principles for management of stable IHD. IRP includes a combination of Snehana (oleation), Swedana (thermal vasodilation) and Basti (per rectal drug administration) administered in the same order. Additionally, herbs used at each of these steps may have an additional cardio-protective effect. This pilot study is a first attempt to find evidence to prove the efficacy of IRP in improving myocardial blood perfusion in stable IHD patients as assessed by SPECT-MPI.

Research Methodology

Study design

The present open-label study screened IHD who were willing to undergo IRP therapy at Madhavbaug clinics in Maharashtra, India.

Inclusion criteria

Patients in the age group between 40-70 years having the clinical diagnosis of known IHD were recruited in the study. Other parameters considered for inclusion in the study were patients with BMI >20kg/m² as well as with stress test positive for inducible ischemia.

Exclusion criteria

Patients with recent myocardial infarction and/or known hypothyroidism or hyperthyroidism or chronic kidney disorder were excluded from the present study.

Patient visit schedule

SPECT-MPI was performed from December 2016 to September 2017 at two centres namely Sushrut Hospital & Research Centre, Chembur and Deenanath Mangeshkar Hospital, Pune. The schedule of the patient visit at study site was as follows:

a. Screening: Stress test positive patient for inducible ischemia were sent for SPECT-MPI.

b. Enrolment: If the SPECT-MPI test was positive, then the patient was enrolled in the study.

c. Treatment:

•After the 1^st SPECT-MPI enrolled patients were given 21 IRP sittings.

•After completion of 21 IRP sittings, the patients were sent for 2^nd SPECT-MPI.

The current study was ethically conducted in accordance with the Declaration of Helsinki, and all patients provided written informed consent.

Other study measurements

Following tests were performed in all patients:

•VO₂ peak measurement was obtained using cardiac stress testing

•Time of ischemia was performed using Modified Bruce Cardiac stress testing

•Seattle Angina Questionnaire (SAQ) was recorded telephonically by research coordinators.

Statistical Analysis

Demographic data namely age and height is reported as Mean ± SD. The distribution of patients based on gender is reported as N (%). Also, the number of patients who had prior PCI or CABG is given as N (%), the primary and secondary endpoints are depicted as Mean ± SD. The change in these endpoints at baseline and after IRP was determined using paired t-test and p<0.05 was considered to be significant. Ischemic burden was calculated using the formula ([summed difference score/68 (maximal segmental score=4)] × 100 = percentage ischemic myocardium). The statistical analysis was performed using SPSS version 21.0.

Results

The current study, 27 patients were screened but only14 IHD patients were enrolled (Figure 1). The average age of study population was 57.5 ± 7.1 years of which eight (57%) were males. Clinical history of enrolled patients is depicted in Table 1. All the patients completed 21 sittings of the IRP therapy. Complete compliance to study protocol was observed.

The Summed Stress Score (SSS) and Difference Score (SDS) obtained after SPECT-MPI showed statistically significant improvement in myocardial perfusion after IRP as compared to baseline i.e., at the time of enrolment (Table 2). Figure 2 depicts one of the SPECT-MPI images showing improvement in myocardial perfusion after 21 IRP sittings as compared to baseline. The patients were further stratified based on their ischemic burden and a reduction in ischemic burden was seen in all the categories as depicted in Table 3.

The VO₂ peak levels and time of ischemia were observed to be increased showing improvement in cardiac muscle activity. The SAQ results also support the improvement in cardiac health (Table 2). However, the ejection fraction score was not found to be significantly changed post-IRP as compared with baseline.

Discussion

This is the first alternative medicine study according to our knowledge reporting the beneficial effect of Ayurveda based therapy on myocardial perfusion in IHD patients as assessed by SPECT-MPI [5].

The study therapy, IRP includes three key panchakarma techniques namely snehana, swedana, and basti which by themselves have health benefits [6,7] but the current therapy also uses herbs in the form of oil and/or water-based decoction that is beneficial especially for cardiac health. Several studies have highlighted the coronary vasodilator and anxiolytic properties of lavender oil used for Snehana [8,9]. Additionally, the herbs used in GHA kadha are known to be cardioprotective in nature. Numerous studies have reiterated that Gokshur (Tribulus terrestris ) has nitric oxide driven vasodilatation effect; Haridra (Curcuma longa ) is known for its anti-inflammatory action and Amalaki (Phyllanthus emblica ) is an antioxidant that helps to reduce endothelial dysfunction [10-13].

The present study used SPECT myocardial perfusion imaging for assessment of the effect of IRP on myocardial perfusion. SPECT MPI is one of the best-known diagnostic and/ or prognostic techniques. Two well-known nuclear sub-studies namely COURAGE [14] and BARI-2D [15] used SPECT-MPI as a diagnostic tool and found it to be helpful in associating reduction in perfusion and efficacy of the treatment modalities namely medical therapy and revascularization used in these trials. The COURAGE sub-study reported added benefit of PCI as compared to optimal medical therapy alone. Further the results also pointed out the PCI may not be an effective treatment choice for patients with no to mild ischemic burden [14]. However, our study showed a beneficial effect of IRP even in patients with a low ischemic burden.

Additionally, an Asian study conducted in patients with IHD underlines utility of MPI for mortality risk stratification irrespective of ethnicity [16]. Another study also revealed the usefulness of SPECT MPI in the elderly population (50 to ≥ 80) in predicting cardiovascular events and accordingly choosing better treatment [17].

The importance of alternative and complementary therapies has been emphasized time and again for various heart diseases. One such study although using different treatment option namely cardiac rehabilitation program in addition to standard treatment also shows improvement in cardiac re-vascularization as shown by SPECT MPI [18].

Conclusion

The present pilot study although with a small sample size shows positive role of IRP in IHD management. A future large trial is warranted to set a concrete foundation for including IRP as a mainstream IHD management therapy in addition to conventional treatment.

Funding

Vaidya Sane Ayurvedic Education and Agricultural Trust.

Previous Presentation

This data has been presented as poster presentation at Heart Failure 2018 & World Congress on Acute Heart Failure.

Conflicts of Interest

Dr. RS and Dr. RM are employees of Vaidya Sane Ayurvedic Education and Agricultural Trust. Dr. JH, Dr. CC, Dr. SN have no conflict of interest to declare.

Acknowledgments

The authors thank Poonam Pawar for writing assistance and editorial support for this manuscript. The authors thank the study participants and their families, without whom this study would not have been accomplished.

References

1. Registrar General of India (2013) Report on Medical Certification of Report on Medical Certification of 2013.
2. Lugomirski P, Chow BJ, Ruddy TD (2014) Impact of SPECT myocardial perfusion imaging on cardiac care. Expert Rev Cardiovasc Ther 12:1247-1249.
3. Georgoulias P, Valotassiou V, Tsougos I, Demakopoulos N (2010) Myocardial perfusion SPECT imaging in patients after percutaneous coronary intervention. Curr Cardiol Rev 6: 98-103.
4. Acampa W, Gaemperli O, Gimelli A, Knaapen P, Schindler TH, et al. (2015) Role of risk stratification by SPECT, PET, and hybrid imaging in guiding management of stable patients with ischaemic heart disease: Expert panel of the EANM cardiovascular committee and EACVI. Eur Heart J Cardiovasc Imaging 16: 1289-1298.
5. Wade M, Li YC, Wahl GM (2013) MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer 13: 83-96.
6. Williamson EM (2004) Scientific basis for Ayurvedic therapies. J Ethnopharmacol 91: 373.
7. Vinjamury SP, Vinjamury M, Sucharitakul S, Ziegler I (2012) Panchakarma: Ayurvedic detoxification and allied therapies-is there any evidence?. InEvidence-based practice in complementary and alternative medicine. Springer, Berlin, Heidelberg.
8. Shiina Y, Funabashi N, Lee K, Toyoda T, Sekine T, et al. (2008) Relaxation effects of lavender aromatherapy improve coronary flow velocity reserve in healthy men evaluated by transthoracic Doppler Echocardiography. Int J Cardiol 129: 193-197.
9. López V, Nielsen B, Solas M, Ramírez MJ, Jäger AK (2017) Exploring pharmacological mechanisms of lavender (Lavandula angustifolia) essential oil on central nervous system targets. Front Pharmacol 8:280.
10. Shukla V, Vashistha M, Singh SN (2009) Evaluation of antioxidant profile and activity of amalaki (Emblica officinalis), spirulina and wheat grass. Indian J Clin Biochem 24: 70-75.
11. Srinivas C, Prabhakaran KV (1989) Haridra (Curcuma longa) and its effect on abhisayanda (conjunctivitis). Anc Sci Life 8: 279.
12. Chhatre S, Nesari T, Kanchan D (2014) Phytopharmacological overview of Tribulusterrestris. Pharmacogn Rev 8: 45.
13. Fatima L, Sultana A, Ahmed S, Sultana S (2015) Pharmacological activities of Tribulus terrestris Linn: A systemic review. World J Pharm Pharm Sci 4: 136-150.
14. Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, et al. (2008) Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden. Circulation 117: 1283-1291.
15. Shaw LJ, Cerqueira MD, Brooks MM, Althouse AD, Sansing VV, et al. (2012) Impact of left ventricular function and the extent of ischemia and scar by stress myocardial perfusion imaging on prognosis and therapeutic risk reduction in diabetic patients with coronary artery disease: Results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. J Nucl Cardiol 19: 658-669.
16. Hori Y, Yoda S, Nakanishi K, Tano A, Suzuki Y, et al. (2015) Myocardial ischemic reduction evidenced by gated myocardial perfusion imaging after treatment results in good prognosis in patients with coronary artery disease. J Cardiol 65: 278-284.
17. Perrone-Filardi P, Cuocolo A, Dellegrottaglie S (2012) Myocardial perfusion imaging in very elderly patients with suspected coronary artery disease: Never too late!. J Nucl Cardiol 2012;19: 224-226.
18. El-Demerdash S, Khorshid H, Salah I, Abdel-Rahman MA, Salem AM (2015) Cardiac rehabilitation improves the ischemic burden in patients with ischemic heart disease who are not suitable for revascularization. Cardiovasc Revascularization Med 16: 280-283.