Diastolic Dysfunction in Individuals With Human Immunodeficiency Virus Infection: Literature Review, Rationale and Design of the Characterizing Heart Function on Antiretroviral Therapy (CHART) Study

Abstract

Antiretroviral therapy (ART) has been associated with a shift in the epidemiology of human immunodeficiency virus (HIV)-associated cardiomyopathy from a phenotype of primarily left ventricular (LV) systolic dysfunction to LV diastolic dysfunction (DD). Patients with HIV receiving ART have higher rates of DD compared with age-matched control subjects and develop DD at a younger age. However, little is known about the natural history and pathogenesis of DD in virally suppressed HIV-infected patients. Current evidence suggests that immune processes modulate the risk for cardiac involvement in HIV-infected persons. Ongoing inflammation appears to have myocardial effects, and accelerated myocardial fibrosis appears to be a key mediator of HIV-induced DD. The Characterizing Heart Function on Antiretroviral Therapy (CHART) study aims to systematically investigate determinants, mechanisms, and consequences of DD in HIV-infected patients. We will compare ART-treated virally suppressed HIV-infected individuals with and without DD and HIV- individuals with DD regarding (1) systemic inflammation, myocardial stress, and subclinical myocardial necrosis as indicated by circulating biomarkers; (2) immune system activation as indicated by cell surface receptors; (3) myocardial fibrosis according to cardiac magnetic resonance examination; (4) markers of fibrosis and remodeling, oxidative stress, and hypercoagulability; (5) left atrial function according to echocardiographic examination; (6) myocardial stress and subclinical necrosis as indicated by circulating biomarkers; (7) proteomic and metabolic profiles; and (8) phenotype signatures derived from clinical, biomarker, and imaging data.

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort

“…That study aims to establish clinical phenotypes of DD in persons with chronic HIV. 29 Finally, the cross-sectional nature of the present study does not address the potential evolution of ventricular dysfunction among PLWH and limits our ability to evaluate the future risk of the evolution of incident clinical heart failure. Although future studies of our cohort will focus on monitoring its members longitudinally to investigate the natural history of ventricular dysfunction in this group, a prospectively identified and followed longitudinal cohort is needed to explore and fully characterize the evolution and determinants of cardiac structural alterations in PLWH.…”

Accumulation of prelamin A drives inflammation in the heart with implications for treatment of inherited and acquired cardiomyopathies

“…Previous studies have identified nucleoside reverse transcriptase inhibitors (NRTIs) used in conjunction with HIV PIs as responsible for the development of cardiomyopathy in HIV patients (24,25). Presently, there is limited knowledge on the impact of HIV PIs on the development of cardiomyopathy though there is an attempt to 'characterise heart function on antiretroviral therapy' with the introduction of the CHART study (26). These points considered, we sought to investigate the extent and effects of prelamin A accumulation in the setting of cardiomyopathy.…”

Heart failure in human immunodeficiency virus-infected patients

“…Ряд исследователей выделяют отдельную форму патологии сердца при ВИЧ-инфекции -ВИЧ-ассоциированную кардиомиопатию, связанную с прямым повреждающим действием ВИЧ-инфекции на миокард, сопровождающимся апоптозом кардиомиоцитов и фибробластов [1]. Поражение сердца при ВИЧ-инфекции имеет многофакторный патогенез, характеризующийся не только прямым повреждающим действием, но и влиянием вторичной инфекции, приводящей к развитию мио-, пери-и эндокардитов, применением антиретровирусной терапии, обладающей кардиотоксическим действием [2,3].…”

“…Вероятность развития сердечной недостаточности со сниженной систолической функцией левого желудочка (ЛЖ) у ВИЧ-инфицированных больных наступает на 10 лет раньше, чем у пациентов без ВИЧ-инфекции [4]. На фоне антиретровирусной терапии формируется ранняя диастолическая дисфункция (ДД) сердца за счет стимуляции миокардиального фиброза [3].…”

“…Следовательно, при таком лечении подавлялось иммуно-опосредованное повреждение кардиомиоцитов и фибробластов. Авторы выявили, что увеличении концентрации NT-proBNP у ВИЧ-инфицированных больных связано с потреблением кокаина, со снижением ФВ ЛЖ, с увеличением ФК ХСН и значительным снижением количества CD4-Т-лимфоцитов в 1 мм 3 . Нами также были получены статистически значимые взаимосвязи ФВ ЛЖ и NT-proBNP c количества CD4-Т-лимфоцитов в 1 мм 3 .…”