Clinical Review

The Burden of Cardiac Complications in Patients with Community-Acquired Pneumonia



Systemic inflammation is the result of several molecules, such as cytokines, chemokines and reactive oxidant species. Reactive oxidant species may determine oxidation of proteins, lipids and DNA, which leads to cell death. The hypothesis also purports that they also cause destabilization of atherosclerotic plaques leading to MIs. Other reactions as a result of inflammation lead to arrhythmias with or without compromised cardiac function, causing congestive heart failure (CHF). For this reason, some authors have approached the pathophysiology of cardiac complications by considering them to be either plaque-related or plaque-unrelated events [9].

A few studies have linked specific inflammatory molecules to cardiac toxicity. NOX2 is chemically unstable and may provoke cellular damage, thus maintaining a certain redox balance is crucial for cardiomyocyte health. In 248 patients with CAP, an elevated troponin T was present in 135 patients and among those, NOX2 correlated with the troponin T values (OR 1.13, 95% CI 1.08–1.17; P < 0.001) [10]. Both disrupting the equilibrium of the redox balance by upregulating NOX2, and finding NOX2 to be associated with troponin T suggest that oxidative stress is implicated in damage to the myocardium during CAP. In another study of 432 patients with CAP, 41 developed atrial fibrillation within 24 to 72 hours of admission and showed higher blood levels of NOX2 than those who had CAP without atrial fibrillation [11]. Oxidative stress has been shown to cause hypertrophy, dysfunction, apoptotic cell death, and fibrosis in the myocardium [12].

Streptococcus pneumoniae may actually evade the immune system and its inflammatory responses in a very precise manner in order to gain entry into cardiomyocytes [13]. S. pneumoniae has a bacterial adhesion, choline-binding protein A (CbpA), and the cell wall contains phosphorylcholine (ChoP). These 2 agents bind to 2 receptors, lamin receptor (LR) and platelet-activating factor receptor (PAFR) on vascular endothelial cells. In this binding process an endothelial protein is activated which causes endocytosis of the bacteria into a clathrin-coated vesicle, by which the S. pneumoniae either gains transport across the endothelial cell to the myocardium on the other side or dies in a phagolysosome ( Figure 1 ). In the absence of infiltrating immune cells, microlesions (scars) are ultimately formed in the cardiomyocytes. The lesions were found in infected mice, rhesus macaques and in humans at autopsy who died from invasive pneumococcal disease [13].

There is likely a high level of variability in how individual patients respond to a predisposing factor for a cardiac complication. For example, one patient may tolerate a mild hypoxia while another is sensitive. The association of inflammatory markers with the presence of cardiac markers, however, would support that once there are systemic reactions, the complications increase. Macrolides, however, were not found to contribute to long-term mortality due to cardiac complications.

Cardiac Complications of CAP

After the H 1N1 influenza outbreak of 1918, it was noted that all-cause mortality increased during the outbreak as did influenza-related deaths. This prompted inquiry as to whether there was an actual association between the outbreak and increased overall mortality, or whether the 2 occurrences were simply coincidental [14]. Near that time, arrhythmias in CAP patients were studied. T-wave changes were found to be associated with CAP [15]. Among 92 patients studied, 449 electrocardiograms (ECGs) were reviewed. T-wave changes were the most common ECG changes. They were found in 5 of 10 of the patients who died, and in 35 of the 82 patients who lived. Twelve living patients had persistent ECG changes, and although they were all thought to have had underlying myocardial disease, 2 of them certainly did as they each had an acute MI (and the ECG was included as a figure for one of them).


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