Acute Intermittent Porphyria Related Abnormalities in Cardiovascular System

Study Overview
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Brief Summary
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This study aims to assess the changes in the cardiovascular system in patients with acute intermittent porphyria (AIP).

Detailed Description
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Porphyrias are heterogeneous group of the disorders of heme biosynthesis. Acute intermittent porphyria (AIP) is the most common acute hepatic porphyria, caused by the mutations in the gene encoding hydroxymethylbilane synthase. Clinical symptoms i.e. abdominal pain, nausea, vomiting, paresis or paralysis, coma and/or mental abnormalities may be induced by many porphyrinogenic factors, such as drugs, alcohol, starvation or stress. The symptoms are often accompanied by tachycardia and elevated blood pressure. Due to the non-specific clinical picture, AIP is often diagnosed too late and causes a threat to the patients' lives. There is a scarcity of data regarding the changes in cardiovascular system in patients with AIP. The aim of this study is to assess the structure and function of heart in patients with this disease. The prevalence of hypertension, cardiac arrhythmias and selected cardiovascular risk factors in patients with AIP will also be evaluated. This is a case-control study with prospective observation of the subgroup of patients examined during the exacerbations of AIP. Specific goals: assessment of the cardiac morphology and function, assessment of the concentrations of markers of myocardial injury (troponin T) and heart failure (NT-proBNP), assessment of the prevalence of cardiac arrhythmias and electrocardiographic abnormalities, assessment of the blood pressure profiles, assessment of selected cardiovascular risk factors, assessment of quality of life, assessment of clinical and biochemical factors associated with the pathological findings in patients with AIP.

Official Title
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Assessment of the Structure and Function of Heart and Selected Cardiovascular Risk Factors in Patients With Acute Intermittent Porphyria

Conditions
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Porphyrias, Hepatic

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute intermittent porphyria (AIP), age 18-65 years, at least one hospitalization due to exacerbation of AIP. Exclusion Criteria: previous myocardial infarction, heart failure of established (other than porphyria) etiology, severe heart valve disease, congenital heart defects, history of myocarditis, pacemaker, hyperthyroidism / hypothyroidism (except for adequate thyroid hormone replacement therapy), chronic advanced lung diseases, lack of consent to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with acute intermittent porphyria (AIP)<br>Patients aged 18-65 (men and women) with acute intermittent porphyria and at least one episode of exacerbation of this disease requiring admission to the hospital | |
| Control group<br>People recruited from the general population and matched by age, sex and body mass index. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with heart failure and left ventricular dysfunction. | Heart failure and left ventricular dysfunction assessed by symptoms and echocardiography. | day 1 and up to 2 years in case of the exacerbation of AIP | 
| Number of participants with hypertension. | Arterial hypertension diagnosed by ambulatory 24-hour blood pressure monitoring. | day 1 and up to 2 years in case of the exacerbation of AIP | 
| Rate of cardiac arrhythmias. | Cardiac arrhythmias observed in 24-hour ECG monitoring. | day 1 and up to 2 years in case of the exacerbation of AIP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with increased concentrations of markers of heart failure. | Concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 125 pg/mL in serum. | day 1 and up to 2 years in case of the exacerbation of AIP | 
| Number of participants with increased concentrations of markers of myocardial injury. | Concentration of high sensitivity troponin T > 14 ng/L in serum. | day 1 and up to 2 years in case of the exacerbation of AIP | 
| Number of participants with chronic kidney disease. | Renal function defined by estimated glomerular filtration rate based on the concentrations of creatinine in serum. | day 1 and up to 2 years in case of the exacerbation of AIP | 
| Number of participants with dyslipidemia. | Dyslipidemia defined as the concentrations of total cholesterol > 190 mg/dL, low density lipoprotein (LDL) cholesterol > 115 mg/dL, high density lipoprotein (HDL) cholesterol < 48 mg/dL (female), < 40 mg/dL (male), triglycerides > 150 mg/dL. | day 1 | 
| Number of participants with diabetes. | Diabetes in anamnesis or the concentration of glycated hemoglobin > 6.5%. | day 1 | 
| Level of quality of life. | Physical and mental components defined by the Short Form 36 survey (SF36). Answers are weighted and transformed into scores in a scale ranging from 0 (the lowest possible level of functioning) to 100 (no restrictions). | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute intermittent porphyria, myocardial injury, heart failure, hypertension, cardiac arrhythmia, cardiovascular risk factors, lipid profile, quality of life