Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma

Pheochromocytoma Clinical Trial

— PheoCard  

Official title:

Prospective Cohort Study of Objective Cardiac and Vascular Changes in Pheochromocytoma and Paraganglioma and Their Reversal Following Curative Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05082311
• Other study ID #: 2018-185-Mch-EXP-4
• Status: Completed
• Start date: January 19, 2019
• Est. completion date: January 31, 2022

Study information

• Verified date: February 2022
• Source: Sanjay Gandhi Postgraduate Institute of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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

Description:

The aim of this research is to study the cardiac and vascular changes in Pheochromocytoma/ Paraganglioma patients and their reversal following curative surgery

This prospective, case-control study is conducted at SGPGIMS, Lucknow, India, tertiary care referral institute, between January 2019 and September 2021 after approval from institutional ethics committee. The study group includes 50 biochemically and histopathology proven PCC /Paraganglioma patients, who after 1 to 3 weeks of α-adrenoceptor blockade with oral prazosin 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.

Two contemporary age- and gender-matched control groups includes 10 newly detected (withtin 3 months) Essential Hypertensive (E-HT) patients, who will undergo treatment with standard anti- HT medications and 10 Healthy individuals (normal in physical examination, ECG , Echo), that include hospital staff nurses, technicians, doctors whom would be requested to volunteer.

METHODOLOGY

Patients in the study group, besides the usual evaluation of PCC, also undergo detailed cardiac and vascular evaluation, at diagnosis, at 7- 10 days of α-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision and in control groups - E-HT controls, cardiac evaluation is done at diagnosis and after 3 months of anti HT medications ; in Healthy individuals, cardiac evaluation is done at the start of study and after 6 months.

The CV 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: January 31, 2022
• Est. primary completion date: November 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 7 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Cardiovascular Morbidity
• Paraganglioma
• Pheochromocytoma

Intervention

Other:
• Observational study
This is an observational study

Locations

Country	Name	City	State
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences	Lucknow	Uttar Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Sanjay Gandhi Postgraduate Institute of Medical Sciences

Country where clinical trial is conducted

India, 

References & Publications (3)

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. — View Citation

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 p — View Citation

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. Ech — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 a-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months after adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months after adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision
Primary	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 a-blockade, and 7 days, 3 and 6 months post surgery
Primary	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 a-blockade, and 7 days, 3 and 6 months post adrenalectomy/ Paraganglioma excision