Akram Y. Elgendy, MD, MRCP, Ahmed Mahmoud, MD, Islam Y. Elgendy, MD,Hend Mansoor, PhD and C. Richard Conti, MD, MACC

1Department of Medicine, University of Florida, Gainesville, FL, USA

2Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA

3Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA

Background

The incidence of spontaneous subarachnoid hemorrhage (SAH) in the United States of America is 9.7 to 100,000 in the adult population [1]. SAH is also associated with a high incidence of in-hospital mortality with a 12–22% range [2–5], particularly within the first 48 h of presentation [6, 7]. Cardiovascular abnormalities as a consequence of SAH had been previously described in the literature, these abnormalities could be manifested by T wave changes or QTc prolongation on electrocardiograms (ECG) [8],elevated cardiac troponin [9], or resting wall motion abnormality (RSWMA) on the Transthoracic echocardiogram (TTE), referred to as neurogenic cardiomyopathy [10, 11]. As a result, there is a higher incidence of mortality among patients who developed neurogenic cardiomyopathy in the settings of SAH [11]. Some reports related those cardiovascular abnormalities only to selected SAH patients’ population i.e. those who had TTE performed, ECGs taken and troponins drawn [6,11–13]. For that purpose, we constructed a retrospective study to assess the cardiovascular abnormalities including ventricular ballooning in patients with spontaneous SAH admitted to our institution.

Materials and Methods

Study Population

All patients with spontaneous SAH admitted to University of Florida, tertiary teaching hospital, from July 1st2011 till May 30th2014 using International Statistical Classifications of Diseases (ICD)-9 code 430 for identification of SAH patients were enrolled.As TTE findings were pertinent to our study, only patients who had a TTE performed during the same 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 institutional review board approved the study. All study data were collected and managed using REDCap electronic data capture tools hosted at University of Florida [14].

Selection of Patients with SAH

Over a three year period, 2058 patients were admitted to the University of Florida with the primary diagnosis of spontaneous SAH. Diagnosis of spontaneous SAH was confirmed by reviewing the computerized tomography (CT) scans reports and admission documentation notes. TTE was performed on 244 patients only. The decision to perform a TTE was totally dependent on the admitting physician’s clinical judgement. Data on baseline characteristics were obtained from the documentation notes including: patients’ age, sex, history of hypertension, diabetes, coronary artery disease,stroke, smoking status and chronic kidney disease.In-hospital mortality was confirmed by a death note recorded by the physician at the time of death.

Cardiovascular Abnormalities Evaluated

In the 244 patients who underwent TTE, the presence of a RSWMA on TTE, ejection fraction (EF),apical ballooning and global hypokinesis were reviewed. A cardiologist, expert in cardiac ultrasound, who was not directly involved in the care of the patient reported the TTE results. Heart rate, QTc and ST segment changes on the ECG were evaluated.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 interval was defined as QTc >450 ms in males and >470 ms in females [15]. Bazett’s Formula was used to calculate the QTc value from the report of first ECG performed after admission [16]. ST elevation was defined as elevation of >1 mm above the J-point in limb leads and 2 mm in chest leads. Troponin T of>0.03 ng/mL was considered as elevated.

Statistical Analysis

Descriptive statistics were performed for the baseline demographics, ECG, TTE, troponin levels and in-hospital mortality. Data was reported as frequencies for categorical variables, as well as mean and standard deviation for continuous variables.

Table 1: Baseline Demographics and Echocardiographic Changes in Patients Admitted with Subarachnoid Hemorrhage and had Transthoracic Echocardiogram Performed.

Results

Baseline Characteristics

In the selected cohort (the 244 patients who underwent TTE), mean age was 59 years with 66% being females. Seventy one percent of the patients were hypertensive and 17% had prior history of coronary artery disease. In-hospital all-cause mortality was 15.6% of the patient population (38 patients)(Table 1).

Cardiovascular Abnormalities

Of the 244 patients in our cohort, 135 had a troponin T level drawn and 50 of those patients (37%)had an elevated troponin T level during their admission with a mean troponin T level of 0.15 ng/mL.A total of 193 patients had an ECG performed during their stay and 152 (79%) of those had abnormal ECG findings. The most common ECG abnormality was prolonged QTc occurring in 95 (49%) of the 193 patients who had ECG. A total of 26 patients(13%) were found to have tachycardia on the ECG.Thirty nine patients (16%) of the 244 patients who had TTE had a RSWMA including apical ballooning, but only five of them (2%) had classical apical ballooning. Aside from apical ballooning, no other takotsubo cardiomyopathy variants were detected.These abnormalities are summarized in Figure 1.

Apical Ballooning

Five patients were diagnosed with apical ballooning, all patients were females with a mean age of 51 years. Four of the five patients had QTc prolongation on ECG. Troponin T level was positive in four patients. All patients had depressed EF with mean EF 27±6%. Repeated TTE was performed at a mean of 12 days and showed improved EF in all patients tested. One of the five patients died in the first 48 h due to the severity of underlying neurological illness (Table 2).

Discussion

Figure 1: Cardiovascular Abnormalities in Patients Admitted with Subarachnoid Hemorrhage and had Transthoracic Echocardiogram Performed During Index Hospitalization.

Only 244 of the 2058 patients (12%) with SAH at the University of Florida underwent TTE during the index hospitalization. Half of this selected cohort had QTc prolongation, 37% of the patients had positive troponin and 16% had RSWMA on TTE, out of those, only five patients had findings of apical ballooning suggesting classical takotsubo cardiomyopathy. Data was not collected on the 1812 patients who did not have TTE performed.This highly selective process was mainly driven by the individual decisions of the primary caring physicians. As a result, not all patients with spontaneous SAH in our institution or patients from previous reports had all three parameters of cardiovascular abnormalities checked during hospitalization; cardiac markers, ECG and TTE [6, 11–13]. Thus the incidence of clinical outcomes might be underestimated and the only way to derive a strong conclusion is to construct a prospective study in which all patients with spontaneous SAH should undergo cardiovascular evaluation by checking all three parameters; troponin, ECG and TTE during index hospitalization.

For better understanding the incidence of apical ballooning as a consequence of SAH; a literature review of the previously reported cohorts was performed [11, 13, 17–21]. After adding our patient population, a total of 121 patients were diagnosed with apical ballooning out of 5153 SAH patients.Among the 121 patients diagnosed with apical ballooning, the age ranged from 45 to 75 years and 79%were females. Troponin level was positive in 82% of the patients. QTc prolongation was the commonest ECG finding found in 47% of the patients. T wave changes occurred in 46% and ST segment changeswere noticed in 37% of the patients. In-hospital mortality of patients diagnosed with apical ballooning in the setting of SAH was 34%.

Table 2: Demographics, Presentation, and Outcomes of Apical Ballooning Patients in the Setting of Aneurysmal Subarachnoid Hemorrhage in our Institution.

Apical ballooning carries a relatively favorable prognosis; however in patients with SAH it may not be benign. SAH alone is not a benign disease process and this makes it difficult to tease out which process is responsible for the outcome. The only way to arrive at reasonable conclusion is to develop a prospective registry to assess the incidence and the outcome of patients with apical ballooning in the setting of SAH.

Conclusion

Cardiovascular abnormalities are relatively common in patients with SAH when studied retrospectively,however the data on cardiovascular manifestations and outcomes might be underestimated. The only way to arrive at a reasonable conclusion is to develop a prospective registry in which all patients with SAH have ECG abnormalities, cardiac markers and TTE checked during index hospitalization.

The incidence of apical ballooning in patients with spontaneous SAH is not common in selected spontaneous SAH patients who undergo TTE.Apical ballooning in the setting of SAH is common in females. Other cardiac abnormalities are somewhat higher in these same patients e.g. ECG changes and elevated troponins.

Conflict of Interest

The authors declare no conflict of interest.

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