Prevalence of Primary Aldosteronism in Hypertensive Patients Presenting With Atrial Flutter or Fibrillation

NCT ID: NCT01267747

Last Updated: 2019-06-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 411 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2018-12-31

Brief Summary

Primary objective of the PAPPHY Study is to establish the prevalence of primary aldosteronism (PA) in consecutive hypertensive patients referred for 'lone' paroxysmal, persistent or permanent atrial flutter or fibrillation (AFF).

Design: cohort multicenter prospective study. State-of-the-art criteria and guidelines were followed for case detection and management of both PA and of AF in all enrolled patients (Funder J. J Clin Endocrinol Metab 2008 and 2016; Kirchhof P. Eur Heart J 2011 and 2016).

Detailed Description

A previous retrospective study documented a 12-fold increase of the risk of AFF in patients with primary aldosteronism (PA) as compared to subjects with primary (essential) hypertension (Milliez 2005). However, being retrospective this investigation could involve a selection bias and therefore is to be regarded as hypothesis-generating rather than a proof-of-concept study.

Hence, based on results of experimental studies, we hypothesize that in a proportion of hypertensive patients presenting with 'lone' PA could be the underlying cause of hypertension leading to AFF. If proven, this hypothesis would imply that an early diagnosis of PA might not only cure PA and hypertension but also prevent AFF in a non negligible number of hypertensive patients.

Primary objective is to establish the prevalence of PA in consecutive hypertensive patients referred for 'lone' paroxysmal, persistent or permanent AFF.

Study design: Prospective multicenter cohort study.

Sample size:

Based on the PAPY study experience and on available data from the literature concerning prevalence studies, we anticipated that the enrolment of at least 1000 consecutive patients will give conclusive evidence on PA prevalence in AFF patients.

Nothwithstanding a long enrolment period (from 2015 to 2018), we were unable to reach the calculated sample size and, therefore, the study was smaller than the size calculated when the PAPPHY study was conceived. In order not to introduce a time-dependent bias associated with an unduly long recruitment with associated changes in practice, it was decided to stop the study upon screening of 411 patients.

Data analysis. Data collection in a specific software, with the database securely stored and analyzed at the core laboratory of the Arterial Hypertension Unit at the University of Padova, Italy.

Experimental Procedures.

Baseline visit

• Clinic evaluation of the patient;
• Collection of demographic data and history;
• Measurement of blood pressure and heart rate;
• Scanning and storage of ECG documenting AFF;
• Echocardiography for measurement of left atrial and aortic diameters, left ventricular thickness and diameters, systolic and diastolic and transmitral Doppler flow velocity indexes;
• Clinical chemistry including serum ions, s-Creatinine, eGFR, HbA1c, microalbuminuria, TSH;
• Measurement of PRA and plasma aldosterone concentration (PAC), under baseline and after captopril challenge, if the patient is not assuming drugs interfering with the renin angiotensin system and eventually after correction of hypokalemia;
• Cardioversion if needed.

Diagnosis of PA in patients with a florid PA phenotype, i.e. a high aldosterone to renin ratio (ARR), e.g. > 100 (in [ng *dl-1 ] * [ng *ml-1 * h-1]) with no further tests, following the Endocrine Society guidelines (Funder J. J Clin Endocrinol Metab 2016) and based on compelling evidence that in these patients the specificity approaches 100%, and the false negative rate 0% (Maiolino G. J Am Heart Assoc 2017).

Exclusion of PA when ARR < 26 and plasma aldosterone concentration (PAC) < 15 ng *dl-1 at the first or a repeated test. In all PA patients presenting with an ARR value in a grey area (i.e. between 26 and 100, and a PAC > 15 ng *dl-1) at the first and a repeated test after further 1 month wash-out, a confirmatory (captopril challenge) test to rule out false positive results (Funder J. J Clin Endocrinol Metab 2016).

At the end of this work-up, computed tomography and adrenal vein sampling in patients with biochemically confirmed PA for PA subtyping.

Diagnosis of aldosterone producing adenoma (APA) confirmed by biochemical cure, e.g. normalization of plasma renin activity (PRA) and aldosterone, after adrenalectomy.

The protocol of the study was revised in 2013 and then in 2015. Herein is reported the last approved version.

Conditions

Atrial Fibrillation; Atrial Flutter; Aldosteronism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Atrial fibrillation or flutter patients

Patients with 'lone' paroxysmal, persistent, or permanent atrial fibrillation

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Unequivocal evidence (by ECG, Holter ECG or medical charts) of AFF (paroxysmal, persistent or permanent) in patients with blood pressure > 140/90 mmHg on at least 3 office measurements, or current use of anti-hypertensive drugs;
• Written informed consent.

Exclusion Criteria

• Patient refusal to participate to the study;
• Moderate-severe valvular or congenital or myocardial heart disease;
• Current abnormal thyroid function;
• Chronic renal failure (sCreatinine > 200 μM or eGFR < 40 ml/min, calculated with MDRD formula);
• Hemochromatosis;
• Alcohol abuse;
• Acute coronary syndrome, or history of CABG, PTCA with/without stenting, acute myocardial infarction;
• Hepatitis C virus and/or B and/or HIV infection;
• Pheochromocytoma and other known secondary forms of arterial hypertension;
• Hemodynamic instability precluding withdrawal of drugs (e.g. β-blockers, ARBs, ACE-I, diuretics), interfering with PRA (or DRA) and aldosterone measurements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Padova

OTHER

Sponsor Role: lead

Responsible Party

Gian Paolo Rossi, MD, FAHA, FACC

MD, FAHA, FACC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gian Paolo Rossi, MD, FAHA

Role: STUDY_DIRECTOR

Department of Medicine -DIMED, University Hospital of Padova, Italy

Locations

Department of Medicine - DIMED, University of Padova, Italy

Padua, , Italy

Department of Medicine - DIMED, University of Padova, Italy

Padua, , Italy

Countries

Italy

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Other Identifiers

GPR-PAPPHY

Identifier Type: -

Identifier Source: org_study_id