Demand Ischemia Could Mean Deadly Consequences in Pneumonia Patients
Epidemiological studies confirm that patients with pneumonia are at an increased risk of myocardial infarction, heart failure, and arrhythmias during the acute episode and up to 10 years thereafter. Patients who develop cardiovascular complications during or after pneumonia are at twice the dying than with the pneumonia alone. The underlying mechanisms of these cardiac events are not fully understood, but recently, a group of investigators from San Antonio, TX, found that Streptococcus pneumoniae, the most frequently isolated bacterial pathogen during pneumonia, can invade the myocardium and disrupt cardiac function in mice with invasive pneumococcal disease. Whether the pneumococcus is capable of escaping from the lungs to generate cardiac complications during severe pneumonia was unclear at the time. However, in the September issue of the Blue Journal, the same group presented evidence that of S. pneumoniae can escape the lungs during pneumonia, invade the heart, kill cardiomyocytes and induce heart scarring thereafter.
In this study, researchers used a non-human primate (NHP) model of pneumococcal pneumonia. The evaluation of cardiac toxicity included electrocardiogram (ECG), transthoracic echocardiogram, and serum biomarkers. Several molecular techniques were used to assess pneumococcal invasion of the heart and its consequences including immunofluorescence staining, transmission electron microscopy (TEM), ELISAs, and western blots, among others.
Non-specific ischemic alterations were detected by ECG (i.e., T wave inversions and ST segment flattering) and in the pre-mortem echocardiogram (i.e., focal wall akinesias). Troponin I levels were statistically significantly higher at the end of the experiment compared to baseline parameters. During the tissue examination, the researchers described, for the first time in the medical literature, that S. pneumoniae is capable of inducing necroptosis (a highly proinflammatory cell-death pathway) in cardiomyocytes during pneumonia. Moreover, collagen deposition (i.e., scar formation) was observed in TEM and picosirius staining due to the up-regulation of the TGF-beta pathway in rescued animals compared to the other animals.
This experimental model of severe pneumococcal pneumonia in NHP shows what we frequently find in patients with pneumonia: non-specific ischemic electrocardiographic changes and mild increase of troponin levels (i.e., demand ischemia). But here, evaluation of the heart demonstrated dead cardiomyocytes, structural damage, and subsequent scar formation only in those treated with antibiotics.
Taken together, these data urge us to remain cognizant of the fact that the “demand ischemia” we see in our patients could have long term adverse cardiac consequences. Moving forward, it will be important to determine whether these mechanisms are pathogen-specific or if necroptosis/scarring in the heart happens in patients with pneumonias of all kinds.
Reference: Reyes LF, Restrepo MI, Hinojosa CA, Soni NJ, Anzueto A, et al. Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling. Am J Respir Crit Care Med. 2017 Sep 1;196(5):609-620. doi: 10.1164/rccm.201701-0104OC. PubMed PMID:28614669.
