Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma

NCT05082311 | Completed DMC

• 1 other identifier: 2018-185-Mch-EXP-4
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

PHEOCHROMOCYTOMA (PCC)/ PARAGANGLIOMA are catecholamine secreting tumors with varied manifestations. Besides hypertension, PCC patients may have subclinical to overt cardiac and vascular dysfunction, which are important to recognize to minimize perioperative morbidity and mortality. Cardiovascular (CV) dysfunction can be in the form of hypertension, left ventricular (LV) hypertrophy, heart failure, cardiomyopathy, dysrhythmias, angina and Myocardial infarction. Literature search revealed a few retrospective and a few prospective studies, including one prospective follow up study conducted at SGPGIMS to document CV changes in PCC. Our institutional study was the first to document the nature and extent of CV dysfunction and cardiomyopathy and their reversal after surgical cure. The studies revealed that PCC patients had significantly higher LV mass index, higher LV diastolic dysfunction, subclinical impaired LV systolic function. Earlier studies postulated apparent improvement in various cardiac indices even with selective α-blockade and continued after surgical cure, with near normalization at 3 -6 months postoperatively. Detailed cardiac and vascular evaluation in PCC patients can be of help in preoperative optimization of cardiac risk and may provide prognostic information The literature on PCC-mediated CV dysfunction and catecholamine cardiomyopathy is largely limited to case reports and retrospective studies, with few reports of their reversal after curative PCC operations. Whether the duration of disease influence the function of heart was not apparently addressed in earlier trials. Trials that established the differences in the degree of cardiac dysfunction between normotensive and hypertensive PCC patients involved smaller proportion of study subjects. Sub clinical changes in endomyocardium was presumed but not objectively assessed and hence its reversal after surgical cure is uncertain. The aim of this research is to study the cardiac and vascular changes in Pheochromocytoma/ Paraganglioma patients and their reversal following curative surgery

Conditions

Pheochromocytoma; Paraganglioma; Cardiovascular Morbidity

Keywords

Pheochromocytoma; Paraganglioma; Cardio vascular manifestations; Cardiomyopathy; Speckle Tracking echocardiography

Outcome Measures

Primary Outcomes (8)

• Change of Systolic function indices measurement by 2D-Echocardiography from Baseline versus after alpha blockade and after surgery

  Left ventricle end systolic and end diastolic diameter in millimeter

  at baseline (Day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision

• Change of Systolic function indices measurement by 2D-Echocardiography from baseline versus after alpha blockade and after surgery

  Left ventricle end systolic and end diastolic volume dimensions in milliliter

  at baseline (day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision

• Change of Systolic function index measurement by 2D-Echocardiography from Baseline at after alpha blockade and at after surgery

  Left ventricle Ejection fraction by Simpsons method in percentage

  at baseline (Day1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision

• Change of Diastolic function index measurement by pulsed wave doppler echocardiography from baseline versus after alpha blockade and after surgery

  Peak velocities of the early (E) and Late phase (A) of the mitral valve inflow pattern and their ratio in centimeter per second

  at baseline (Day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months after adrenalectomy/ Paraganglioma excision

• Change of Diastolic function indices measurement by pulsed wave doppler echocardiography from baseline versus after alpha blockade and after surgery

  Flow rate across mitral valve in centimeter per second and deceleration time in millisecond

  at baseline (day 1), at day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months after adrenalectomy/ Paraganglioma excision

• Change in Speckle tracking echocardiographic parameters at Baseline versus after alpha blockade and at after surgery

  Left ventricle global longitudinal strain in percentage

  at baseline (Day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision

• Change in Speckle tracking echocardiographic parameters from Baseline in comparison to after alpha blockade and after surgery

  Left ventricle global circumferential strain in percentage

  at baseline (Day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post surgery

• Change in Vascular Function indices by doppler Ultrasonography of the brachial artery from baseline at after alpha blockade and at after surgery

  Flow mediated dilation of brachial artery diameter pre and post sublingual isosorbide dinitrate in millimeter

  at baseline (Day 1), at Day 7- 10 after initiation of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision

Study Arms (3)

Patients with Pheochromocytoma/Paraganglioma (secretory, extra adrenal pheochromocytoma)

Patients included in this cohort (n=50) are those who are diagnosed of Pheochromocytoma / Paraganglioma, willing to consent for the study and not on α-blockade at the time of recruitment into study, while can be on any other anti hypertensives Patients in this group, besides the usual evaluation of Pheochromocytoma / Paraganglioma, will also undergo detailed cardiac and vascular evaluation, which will be done at diagnosis, at 7- 10 days of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision The cardiovascular evaluation includes 2D-echocardiography, speckle tracking Echo (for measuring global longitudinal strain), serum NT-proBNP estimation and flow mediated vasodilatory studies by Doppler Ultrasonography of the brachial artery to assess the endothelial dependent and smooth muscle dependent vasodilatory responses

Other: Observational study

Essential Hypertensive Groups

This is a contemporary age- and gender-matched control group This group includes 10 newly detected (within 3 months) Essential Hypertensive patients, who will undergo treatment with standard anti- HT medications Cardiac evaluation will be done at baseline and after 3 months of anti hypertensive medications

Other: Observational study

Healthy Individuals

This is a contemporary age- and gender-matched control group This group includes 10 Healthy individuals (normal in physical examination, ECG , Echo), that include hospital staff nurses, technicians, doctors whom would be requested to volunteer Cardiac evaluation will be done at the start of study and after 6 months

Other: Observational study

Interventions

Observational study OTHER

This is an observational study

Essential Hypertensive Groups; Healthy Individuals; Patients with Pheochromocytoma/Paraganglioma (secretory, extra adrenal pheochromocytoma)

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study group will include 50 biochemically and histopathology proven Pheochromocytoma /Paraganglioma patients, who after 1 to 3 weeks of α-adrenoceptor blockade with oral prazosin will undergo primary laparoscopic or open surgery. Cure of hypercatecholaminism will be documented by normal 24-hour urinary fractionated metanephrine values at 7-10 days postoperatively.

You may qualify if:

• Patients diagnosed of Pheochromocytoma (PCC) / Paraganglioma (secretory, extra adrenal PCC) Patients willing to consent for the study Patients not on α-blockade at the time of recruitment into study, can be on any other anti hypertensives

You may not qualify if:

• Non-secretory Paraganglioma Patients who refuse consent, not compliant in follow up Patients who are on α- blockade already Essential Hypertensives with compounding comorbidities that could interfere with cardio vascular evaluation

Sponsors & Collaborators

• Sanjay Gandhi Postgraduate Institute of Medical Sciences: lead

Study Sites (1)

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, 226014, India

Location

Related Publications (4)

• Agarwal G, Sadacharan D, Kapoor A, Batra A, Dabadghao P, Chand G, Mishra A, Agarwal A, Verma AK, Mishra SK. Cardiovascular dysfunction and catecholamine cardiomyopathy in pheochromocytoma patients and their reversal following surgical cure: results of a prospective case-control study. Surgery. 2011 Dec;150(6):1202-11. doi: 10.1016/j.surg.2011.09.001.

  PMID: 22136841 RESULT

• Agarwal G, Mishra AK, Kapoor A, Agarwal A, Bhatia E, Mishra SK. Reversal of catecholamine induced cardiomyopathy in a patient with bilateral malignant pheochromocytoma. J Assoc Physicians India. 2001 Dec;49:1193-6.

  PMID: 11996444 RESULT

• Ding L, Zhu WL, Zeng ZP, Li HZ, Ji J, Fang LG, Sun JP. Subclinical left ventricular systolic dysfunction detected by two-dimensional speckle tracking echocardiography in patients with pheochromocytoma and paraganglioma and preserved ejection fraction. Echocardiography. 2018 Feb;35(2):184-189. doi: 10.1111/echo.13752. Epub 2017 Nov 22.

  PMID: 29168209 RESULT

• Vishvak Chanthar KMM, Khanna R, Agarwal G, Rout SR, Kapoor A, Sabaretnam M, Chand G, Mishra A, Agarwal A, Mishra SK. Cardiac Changes and Their Reversal Following Curative Surgery in Pheochromocytoma: PheoCard Prospective Cohort Study. World J Surg. 2023 Feb;47(2):304-311. doi: 10.1007/s00268-022-06731-6. Epub 2022 Oct 10.

  PMID: 36210362 DERIVED

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Cardiomyopathies

Interventions

Observation

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Gaurav Agarwal, MS,DNB,PDC

  Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Endocrine Surgery

Study Record Dates

• First Submitted: July 25, 2021
• First Posted: October 18, 2021
• Study Start: January 19, 2019
• Primary Completion: November 30, 2021
• Study Completion: January 31, 2022
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

IN (1)