Myocardial Protection in Patients With Post-acute Inflammatory Cardiac Involvement Due to COVID-19

Summary

Long COVID or Postacute sequelae of COVID-19 infection (PASC) are increasingly recognised complications, defined by lingering symptoms, not present prior to the infection, typically persisting for more than 4 weeks. Cardiac symptoms due to post-acute inflammatory cardiac involvement affect a broad segment of people, who were previously well and may have had only mild acute illness (PASC-cardiovascular syndrome, PASC-CVS). Symptoms may be contiguous with the acute illness, however, more commonly they occur after a delay. Symptoms related to the cardiovascular system include exertional dyspnoea, exercise intolerance chest tightness, pulling or burning chest pain, and palpitations (POTS, exertional tachycardia).

Pathophysiologically, Long COVID relates to small vessel disease (endothelial dysfunction) vascular dysfunction and consequent tissue organ hypoperfusion due to ongoing immune dysregulation. Active organs with high oxygen dependency are most affected (heart, brain, kidneys, muscles, etc.). Thus, cardiac symptoms are often accompanied by manifestations of other organ systems, including fatigue, brain fog, kidney problems, myalgias, skin and joint manifestations, etc, now commonly referred to as the Long COVID or PASC syndrome.

Phenotypically, PostCOVID Heart involvement is characterised by chronic perivascular and myopericardial inflammation. We and others have shown changes using sensitive cardiac MRI imaging that relate to cardiac symptoms (Puntmann et al, Nature Medicine 2022; Puntmann et al, JAMA Cardiol 2020; Summary of studies included in 2022 ACC PostCOVID Expert Consensus Taskforce Development Statement, JACC 2022, references below).

Early intervention with immunosuppression and antiremodelling therapy may reduce symptoms and development of myocardial impairment, by minimising the disease activity and inducing disease remission. Low-dose maintenance therapy may help to maintain the disease activity at the lowest possible level. The benefits of early initiations of antiremodelling therapy to reduce symptoms of exercise intolerance are well recognised, but not commonly employed outside the classical cardiology contexts, such as heart failure or hypertension. As most patients with inflammatory heart disease only have mild or no structural abnormalities, they are left untreated (standard of care).

The aim of this study is to examine the efficacy of a combined immunosuppressive / antiremodelling therapy in patients with PASC symptoms and inflammatory cardiac involvement determined by CMR, to reduce the symptoms and inflammatory myocardial injury and thereby stop the progression to reduced LVEF, HF and death.

Conditions

• COVID-19 Associated Cardiac Involvement
• Remodeling, Left Ventricle
• Remodeling, Vascular
• Left Ventricular Dysfunction
• Exercise Intolerance
• Vascular Inflammation
• Microvascular Angina
• Long COVID
• Myocarditis, Pericarditis

Interventions

DRUG

Prednisolone

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

DRUG

Losartan

randomised double-blind, placebo-controlled clinical trial 1:1 randomisation

Sponsors & Collaborators

• Bayer

  collaborator INDUSTRY

• Alcedis GmbH

  collaborator INDUSTRY

• Valentina Puentmann

  lead OTHER

Principal Investigators

• Valentina Puntmann, MD, PhD · Goethe University Frankfurt

• Eike Nagel, MD, PhD · Goethe University Frankfurt

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-12-12

Primary Completion

2025-08-08

Completion

2026-03-31

Countries

• Austria
• Germany

Study Locations