This retrospective analysis illustrates the prognostic significance of prolonged QTc, in relation to in-hospital all-cause mortality in patients with spontaneous SAH. The presence of prolonged QTc interval was associated with a five-times-increased risk of death in SAH patients, compared to those with normal QTc interval. This concurs with the previous studies that evaluated prolonged QTc interval prognostic significance [7, 8]. Ichinomiya et al. reached a conclusion similar to ours; however, they used the Glasgow Outcome Scale at hospital discharge, as a primary outcome, rather than in-hospital mortality. They found that a QTc of 448 ms at day 7 of admission was 73% sensitive (95% CI 68–78%) and 93% specific (95% CI 90–96%) prognostic tool to detect such outcome . Marafioti et al. reported that prolonged QTc was an independent prognostic tool for detection of index mortality in SAH patients when it was compared to other prognostic risk factors such as clinical and CT grading of SAH. Most of the other cardiovascular abnormalities found in SAH such as T-wave inversion, ST changes, and RSWMA, were not reported in that analysis .
This study was not designed to address the pathophysiology behind prolonged QTc association with increased short-term all-cause mortality. However, the association might be explained by either a causal relationship, where prolonged QTc increases the chances of developing ventricular arrhythmias and thus sudden cardiac death , or the prolonged QTc could be just a reflection of severe SAH grade, which is associated with poor prognosis [7, 8]. A prospective study by Frontera et al. illustrated the prognostic significance of arrhythmia (including atrial fibrillation, atrial flutter, and sustained ventricular tachycardia) in SAH patients, showing an increased risk of mortality compared to those with normal heart rhythm (OR 8.0, 95% CI 1.9–34.0, p = 0.005) .
In a multicenter prospective study by van der Bilt, et al. , RSWMA was found to be the only prognostic indicator of short-term mortality, while other cardiovascular abnormalities including QTc prolongation, elevated troponins, or proBNP, lost their significance on multivariable regression analysis. Although our study reached a different conclusion, multiple considerations should be pointed out. First, that study primarily enrolled patients with mild clinical grading, and thus patients who might have the highest risk of in-hospital mortality were excluded. Also, it was not clear, from their method, how the QTc interval was analyzed and if it was incorporated in the multivariable regression analysis or not. Finally, their primary outcome was delayed cerebral ischemia while mortality at 3 months was reported as a secondary outcome, rather than index hospitalization mortality.
Elevated troponin level increased the risk of in-hospital death in our study by univariate analysis; however, this risk lost its significance after the multivariable regression analysis. This observation concurs with some of the previous studies [1, 11]. Meanwhile, studies reporting elevated troponin as a prognostic risk factor for mortality were not adjusted for other cardiovascular abnormalities [10, 20]. In addition, echocardiographic features of takotsubo cardiomyopathy have been linked to worse outcomes ; however, owing to the small number of patients who had findings of takotsubo syndrome (i.e., five patients), thus our study could not confirm this association.
Limitations of our study include: first, as a tertiary center we were more likely to have more complex patients, compared to non-tertiary hospital SAH population, however, no patients were excluded because of severity of SAH. Second, there were missing data regarding some of the cardiovascular abnormalities collected, including troponin levels and ECG reports; however, we do not believe that those were not large enough to affect our final analysis. Third, QTc interval was calculated by computer, which used Bazett’s formula. Bazett’s formula at best may be imprecise; however, it remains the simplest and most applicable formula for calculation of QTc . Finally, the confidence interval for prolonged QTc association with in-hospital mortality is wide, which might be due to our sample size, and thus any conclusion drawn from our study needs to be confirmed in a larger patient population.