Cardiovascular Abnormalities and in-Hospital All-Cause Mortality in Patients with Spontaneous Sub-Arachnoid Hemorrhage: An Observational Study

All patients with SAH admitted to the University of Florida, a tertiary academic hospital, from July 2011 until May 2014, using International Statistical Classifications of Diseases (ICD)-9 code 430, for identification of SAH patients, were enrolled. As transthoracic echocardiogram (TTE) findings were pertinent to our study, only patients who had a TTE performed during the admission were included. TTE was identified by the Current Procedural Terminology (CPT) code 93303. Patients <18 years old, patients mislabeled as SAH, or those with traumatic SAH were excluded from the study. The diagnosis of spontaneous SAH was confirmed by reviewing the computerized tomography (CT) scan reports and the admission documentation notes.

The following data were obtained: patients’ age, sex, history of hypertension, diabetes, coronary artery disease, prior stroke, smoking status, chronic kidney disease, baseline Hunt-Hess score (from I to V) [12] and CT scan Fisher grading for SAH (from 1 to 4) [13]. Based on the heart rate measured on the first ECG report, we categorized the patients’ rhythm into: tachycardia (>100 bpm), normal (60–100 bpm), and bradycardia (<60 bpm). A prolonged QTc was defined as QTc interval >450 ms in males and >470 ms in females [14]. Bazett’s formula was used to calculate the QTc value from the report of first ECG performed after admission [15]. ST elevation was defined as elevation of >1 mm above the J-point in limb leads and 2 mm in chest leads. Ejection fraction was divided into: >55%, 35–55%, and <35%. The presence and location of RSWMA, apical ballooning, and global hypokinesis was also recorded. A cardiologist, expert in cardiac ultrasound, who was not directly involved in the study, reported the TTE results. Highly sensitive troponin T is the cardiac biomarker of choice in our institution, with a reference range of <0.03 ng/ml, thus 0.03 ng/ml and above was considered as elevated troponin T level. In-hospital mortality was confirmed by a death note recorded by the physician at the time of death. All study data were collected and managed using REDCap electronic data capture tools hosted at the University of Florida [16]. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. The study protocol was approved by the University of Florida Institutional Review Board, which has waived the informed consent given the retrospective nature of the study.

Descriptive statistics was performed for the baseline demographics, ECG, TTE, troponin levels, and in-hospital mortality. Data were reported as frequencies for categorical variables, as well as mean and standard deviation for continuous variables. Logistic regression with robust standard errors [17] for the estimation of the odds ratio was performed to identify the significant predictors of in-hospital mortality. A final multivariate model included the significant predictors of in-hospital mortality. Results were reported as odds ratio (OR), and corresponding 95% confidence intervals (CI) for the cardiovascular abnormalities. Data analysis was conducted using SAS version 9.4 software (SAS Institute Inc., Cary, NC, USA).

The study initially enrolled 2058 patients with SAH, 295 of them had a TTE performed during the hospitalization. Forty-nine patients had either traumatic SAH or were mislabeled as SAH and thus were excluded from the study. A total of 244 patients were included in the final analysis. The mean age was 59 years, with two-thirds of the patients being females. The majority of the patients had a clinical (Hunt–Hess) grading of II–IV and a CT Fisher grading of 2. In-hospital all-cause mortality was 15.6% of the patient population (Table 1). Compared to the SAH survivors, the deceased patients were older (p = 0.009), with a history of coronary artery disease (p = 0.02), higher Hunt-Hess grade (p < 0.001), and higher incidence of hydrocephalus (p = 0.021) (Table 2).

One hundred thirty-five patients had a troponin level drawn, 37% of those patients had an elevated troponin level during their admission (50 patients), with a mean peak troponin value of 0.15. Meanwhile, 193 patients had an ECG performed during their stay; 78% of those had an abnormal ECG finding (152 patients). The commonest ECG abnormality was prolonged QTc occurring in 57% (95 patients); 13% (26 patients) were found to have tachycardia. Sixteen percent of the total patient population (39 patients) had a RSWMA on TTE, and five patients were found to have findings compatible with takotsubo syndrome (Table 1).

On univariate analysis, prolonged QTc (p < 0.005), elevated troponin level (p = 0.03), EF < 35% (p = 0.03), and RSWMA (p = 0.03) were associated with an increased risk of in-hospital all-cause mortality. However, T-wave inversion (p = 0.12), ST elevation (p = 0.22), and tachycardia (p = 0.24) were not significantly associated with increased mortality (Table 3). On multivariable regression analysis, prolonged QTc was the only cardiac abnormality that was associated with increased in-hospital mortality (OR 5.1, 95% CI 1.04–25.28, p = 0.04) (Table 4).