GENETIC BASIS of LEFT VENTRICULAR APICAL HYPOPLASIA

Brief summary Left ventricular apical hypoplasia (LVAH) is a rare cardiomyopathy characterized by a spherical, truncated LV with some degree of systolic dysfunction, an elongated, normally functioning right ventricle that wraps around the distal left ventricle, deficiency of the myocardium within the LV apex with adipose tissue infiltrating the apex and origin of the papillary muscle in the flattened anterior apex. This condition presents with different clinical presentation, ranging from no symptoms to congestive heart failure or malignant tachycardia. The etiology of this condition is currently unknown. The aim of this study is to evaluate the clinical and genetic characteristics of patients with LVAH.

Background Left ventricular apical hypoplasia (LVAH) is described as congenital heart disease with an unusual type of cardiomyopathy that was first described in 2004 by Fernandez-Valls et al. It is an extremely rare disease; to date, only more than twenty cases were described.

The typical imaging features of this cardiomyopathy include: a spherical, truncated LV with some degree of systolic dysfunction; an elongated, normally functioning right ventricle that wraps around the distal left ventricle; deficiency of the myocardium within the LV apex with adipose tissue infiltrating the apex; origin of the papillary muscle in the flattened anterior apex. A 2D echocardiogram and cardiac MRI can successfully indicate different morphological features This rare phenomenon frequently presents with different clinical manifestations according to the age of the disease, from no symptoms in children to congestive heart failure, pulmonary edema, or even malignant tachycardia in adults. Congenital or genetical etiology was proposed to explain the development of this rare cardiomyopathy.

The aim of this study is to evaluate the clinical and genetic characteristics of patients with LVAH.

Methods Study population

The study population is composed by consecutive patients with diagnosis of LVAH. Diagnosis of LVAH is based on echocardiographic or cardiac magnetic resonance (CMR) evidence of all the following diagnostic criteria:

• a spherical, truncated LV with some degree of systolic dysfunction;
• an elongated, normally functioning right ventricle that wraps around the distal left ventricle;
• deficiency of the myocardium within the LV apex with adipose tissue infiltrating the apex;
• origin of the papillary muscle in the flattened anterior apex. Patients enrolled followed a common protocol designed by GL (Monaldi Hospital, AORN Colli, University of Campania "Luigi Vanvitelli"). The study protocol was approved, and written informed consent was obtained from each subject, according to the procedure established by the Ethic Committee of our institution.

Study protocol Patients enrolled underwent a comprehensive clinical-genetic evaluation commonly practiced in our cardiology division. In particular, the basal evaluation, consisted family and personal history, physical examination, blood tests, 12-lead electrocardiogram (ECG) at rest, conventional M-mode, two-dimensional and Doppler echocardiography, 24-hour Holter ECG, and cardiac magnetic resonance (CMR), and genetic testing with whole exome sequencing (WES). Moreover, all patients are clinically revaluated every 6-12 months.

Study Overview

• Status: Recruiting
• Conditions: Left Ventricular Apical Hypoplasia (LVAH), New Rare Condition

• Study Type: Observational
• Enrollment (Anticipated): 7

Contacts and Locations

• Study Contact: Name: Giuseppe Limongelli, phd,md; Phone Number: 3776902779; Email: limongelligiuseppe@libero.it
• Study Contact Backup: Name: MARTINA CAIAZZA, BMC; Phone Number: 3391574484; Email: martina.caiazza@yahoo.it

Study Locations

• Italy
  • Naples, Italy, 80121
    • Recruiting
    • Ospedale V. Monaldi, Università degli studi della Campania, Luigi Vanvitelli
    • Contact: Giuseppe Limongelli, phd,md; Phone Number: 3776902779; Email: limongelligiuseppe@libero.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 86 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population is composed by consecutive patients with diagnosis of LVAH. Diagnosis of LVAH is based on echocardiographic or cardiac magnetic resonance (CMR) evidence of all the following diagnostic criteria:

• a spherical, truncated LV with some degree of systolic dysfunction;
• an elongated, normally functioning right ventricle that wraps around the distal left ventricle;
• deficiency of the myocardium within the LV apex with adipose tissue infiltrating the apex;
• origin of the papillary muscle in the flattened anterior apex. Patients enrolled followed a common protocol designed by GL (Monaldi Hospital, AORN Colli, University of Campania "Luigi Vanvitelli"). The study protocol was approved, and written informed consent was obtained from each subject, according to the procedure established by the Ethic Committee of our institution.

Description

Inclusion Criteria:

• Male and female patients, 0-90 years old, in any distribution.

• Patients who have the diagnostic criteria for LVAH. Diagnosis of LVAH is based on echocardiographic or cardiac magnetic resonance (CMR) evidence of all the following diagnostic criteria:

  • a spherical, truncated LV with some degree of systolic dysfunction;
  • an elongated, normally functioning right ventricle that wraps around the distal left ventricle;
  • deficiency of the myocardium within the LV apex with adipose tissue infiltrating the apex;
  • origin of the papillary muscle in the flattened anterior apex.

Exclusion Criteria:

• Involvement with any other ongoing studies.
• Patients who have diagnosis of other Cardiomyopathies

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
new gene of LVAH	the principal aim of the study is to identify the new gene of LVAH and to investigate on genetic background of this clinical condition	one year later the completation study

Collaborators and Investigators

• Sponsor: Monaldi Hospital
• Collaborators: Bambino Gesù Hospital and Research Institute

Study record dates

Study Major Dates

• Study Start: September 20, 2013
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 6, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2020
• Last Update Submitted That Met QC Criteria: April 8, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Genetic testing; Left ventricular apical hypoplasia (LVAH); Congenital or genetical condition
• Additional Relevant MeSH Terms: Pathologic Processes; Disease
• Other Study ID Numbers: LVAH_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No