Alexander Kopelnik

Predictors of Neurocardiogenic Injury After Subarachnoid Hemorrhage

Background and Purpose— Subarachnoid hemorrhage (SAH) frequently results in myocardial necrosis with release of cardiac enzymes. Historically, this necrosis has been attributed to coronary artery disease, coronary vasospasm, or oxygen supply-demand mismatch. Experimental evidence, however, indicates that excessive release of norepinephrine from the myocardial sympathetic nerves is the most likely cause. We hypothesized that myocardial necrosis after SAH is a neurally mediated process that is dependent on the severity of neurological injury. Methods— Consecutive patients admitted with SAH were enrolled prospectively. Predictor variables reflecting demographic (age, sex, body surface area), hemodynamic (heart rate, systolic blood pressure), treatment (phenylephrine dose), and neurological (Hunt-Hess score) factors were recorded. Serial cardiac troponin I measurements and echocardiography were performed on days 1, 3, and 6 after enrollment. Troponin level was treated as a dichotomous outcome variable. We performed univariate and multivariate analyses on the relationships between the predictor variables and troponin level. Results— The study included 223 patients with an average age of 54 years. Twenty percent of the subjects had troponin I levels >1.0 &mgr;g/L (range, 0.3 to 50 &mgr;g/L). By multivariate logistic regression, a Hunt-Hess score >2, female sex, larger body surface area and left ventricular mass, lower systolic blood pressure, and higher heart rate and phenylephrine dose were independent predictors of troponin elevation. Conclusions— The degree of neurological injury as measured by the Hunt-Hess grade is a strong, independent predictor of myocardial necrosis after SAH. This finding supports the hypothesis that cardiac injury after SAH is a neurally mediated process.

Acute Neurocardiogenic Injury After Subarachnoid Hemorrhage

Background— Left ventricular (LV) systolic dysfunction has been reported in humans with subarachnoid hemorrhage (SAH), and its underlying pathophysiology remains controversial. Possible mechanisms include myocardial ischemia versus excessive catecholamine release from sympathetic nerve terminals. Methods and Results— For 38 months, echocardiography and myocardial scintigraphy with technetium sestamibi (MIBI) and meta-[123I]iodobenzylguanidine (MIBG) were performed on 42 patients admitted with SAH to assess myocardial perfusion and sympathetic innervation, respectively. A blinded observer interpreted the scintigraphic images. Cardiac troponin I (cTI) was measured to quantify the degree of myocyte necrosis. Blinded observers calculated the LV ejection fraction and graded each LV segment as normal (score=1), hypokinetic (score=2), or akinetic (score=3). A wall-motion score was calculated by averaging the sum of the 16 segments. All subjects with interpretable scans (N=41) had normal MIBI uptake. Twelve subjects had either global (n=9) or regional (n=3) absence of MIBG uptake. In comparison with patients with normal MIBG uptake, those with evidence of functional denervation were more likely to have LV regional wall-motion abnormalities (92% versus 52%, P=0.030) and cTI levels >1 &mgr;g/L (58% versus 21%, P=0.029). Conclusions— LV systolic dysfunction in humans with SAH is associated with normal myocardial perfusion and abnormal sympathetic innervation. These findings may be explained by excessive release of norepinephrine from myocardial sympathetic nerves, which could damage both myocytes and nerve terminals.

Predictors of left ventricular regional wall motion abnormalities after subarachnoid hemorrhage.

IntroductionCardiac abnormalities that have been reported after subarachnoid hemorrhage (SAH) include the release of cardiac biomarkers, electrocardiographic changes, and left ventricular (LV) systolic dysfunction. The mechanisms of cardiac dysfunction after SAH remain controversial. The aim of this study was to determine the prevalence of LV regional wall motion abnormalities (RWMA) after SAH and to quantify the independent effects of specific demographic and clinical variables in predicting the development of RWMA.MethodsThree hundred patients hospitalized with SAH were prospectively studied with serial echocardiography. The primary outcome measure was the presence of RWMA. The predictor variables included the admission Hunt & Hess grade, age, gender, cardiac risk factors, aneurysm location, plasma catecholamine levels, cardiac troponin I (cTi) level, heart rate (HR), blood pressure, and phenylephrine dose. Univariate and multivariate logistic regression was performed with adjustment for serial measurements, reporting olds ratios (OR) and 95% confidence intervals (CI).ResultsIn this study, 817 echocardiograms were analysed. RWMA were detected in 18% of those studied. The prevalence of RWMA in patients with Hunt & Hess grades 3–5 was 35%. Among patients with a peak cTi level grater than 1.0 μg/L, 65% had RWMA. Multivariate analysis demonstrated that high Hunt & Hess grade (OR 4.22 for grade 3–5 versus grade 1–2, p=0.046), a cTi level greater than 1.0 μg/L (OR 10.47, p=0.001), a history of prior cocaine or amphetamine use (OR 5.50, p=0.037), and higher HR (OR 1.34 per 10 bpm increase, p=0.024) were predictive of RWMA.ConclusionsRWMA were frequent after SAH. High-grade SAH, an elevation in cTi levels, a history of prior stimulant drug use, and tachycardia are independent predictors of RWMA.

Cardiovascular predictors of in-patient mortality after subarachnoid hemorrhage

Background and PurposeWhether cardiac dysfunction contributes to morbidity and mortality after subarachnoid hemorrhage (SAH) remains controversial. The objective of this study was to test the hypothesis that cardiovascular abnormalities are independently related to in-patient mortality after SAH.MethodsThis was a prospective cohort study of patients with aneurysmal SAH. Heart rate and blood pressure were measured, a blood sample was obtained, and echocardiography was performed on three study days, starting as soon after admission as possible. The cardiovascular predictor variables were heart rate, systolic blood pressure (SBP), cardiac troponin I (cTi) level, B-type natriuretic peptide (BNP) level, and left ventricular ejection fraction. The primary outcome measure was in-patient mortality. The association between each predictor variable and mortality was quantified by multivariate logistic regression, including relevant covariates and reporting odds ratios (OR) and 95% confidence intervals (CI).ResultsThe study included 300 patients. An initial BNP level greater than 600 pg/mL was markedly associated with death (OR 37.7, p<0.001). On the third study day (9.1±4.1 days after SAH symptom onset), a cTi level greater than 0.3 mg/L (OR 7.6, p=0.002), a heart rate of 100 bpm or greater (OR 4.9, p=0.009), and a SBP less than 130 mmHg (OR 6.7, p=0.007) were significantly associated with death.ConclusionsCardiovascular abnormalities are independent predictors of in-patient mortality after SAH. Though these effects may be explained by a reduction in cerebral perfusion pressure or other mechanisms, further research is required to determine whether or not they are causal in nature.

Prevalence and implications of diastolic dysfunction after subarachnoid hemorrhage

Introduction: Electrocardiographic changes, troponin release, and reduced left ventricular ejection fraction have been described after subarachnoid hemorrhage (SAH). Little is known about the occurrence of diastolic dysfunction in this setting. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with cardiac outcomes after SAH.Methods: SAH patients were prospectively enrolled into the study, and echocardiographic, clinical, chest X-ray, and cardiac troponin I data were obtained on days 1, 3, and 6 after enrollment. Each echocardiogram included Doppler recordings of mitral inflow and pulmonary venous flow. For each study, diastolic function was categorized as normal, impaired relaxation, pseudonormal, or restrictive. The relationships between diastolic dysfunction and pulmonary edema-elevated cardiac troponin I and left ventricular contractile dysfunction were quantified using both univariate and multivariate statistical methods. Clinical predictors of diastolic dysfunction were defined by multivariate logistic regression.Results: Of 223 enrolled subjects, 207 had technically adequate Doppler data. Diastolic dysfunction was observed in 71% of subjects. The prevalence of diastolic versus systeolic dysfunction in 44 patients with pulmonary edema was 91 versus 37%, respectively (p=0.001). After multivariate statistical adjustment, diastolic dysfunction remained a significant predictor of pulmonary edema (odds ratio [OR] 3.34, 95% CI=1.05−10.59). Diastolic dysfunction also was associated with troponin release (p=0.02). A history of hypertension and increasing age were predictive of diastolic dysfunction.Conclusion: Diastolic dysfunction is common after SAH. It is associated with history of hypertension and older age and may explain the development of pulmonary edema in many SAH patients.

Hypernatremia Predicts Adverse Cardiovascular and Neurological Outcomes After SAH

IntroductionAbnormalities of serum sodium are common after subarachnoid hemorrhage (SAH) and have been linked to poor outcome. This study analyzed whether abnormal serum sodium levels are associated with cardiac outcomes and mortality after subarachnoid hemorrhage (SAH).MethodsIn a prospective cohort study of SAH patients, the primary predictor variable was subjects sodium level. Hypernatremia was defined as sodium >143 mmol/L and hyponatremia was <133 mmol/L. Cardiac troponin I (cTi) was measured and echocardiography was performed on three study days. Dichotomous outcome variables were cTi >1.0 μg/L, left-ventricular ejection fraction (LVEF) <50%, presence (vs absence) of regional wall motion abnormalities (RWMA) of the LV, pulmonary edema, and death. Additional analyses studied the degree of hypernatremia and sodium supplementation, and the temporal relationship between hypernatremia and cardiac outcomes.ResultsThe study included 214 subjects. Forty-eight subjects (22%) were hypernatremic on at least one study day, and 45 (21%) were hyponatremic. After multivariate adjustment, hypernatremia was an independent predictor of LVEF <50% (OR 4.7, CI 1.3–16.2, p=0.015), elevated cTi (OR 3.7, CI 1.2–11.9, p=0.028), and pulmonary edema (OR 4.1 CI 1.4–1.5, p=0.008). It was not, however a statistically significant predictor of mortality (p=0.075).ConclusionIn the acute period after SAH, hypernatremia is associated with adverse cardiac outcomes and death. SAH patients with hypernatremia should be monitored for evidence of cardiac dysfunction.

Cardiac injury after subarachnoid hemorrhage is independent of the type of aneurysm therapy.

OBJECTIVE:Subarachnoid hemorrhage (SAH) is associated with cardiac injury and dysfunction. Whether aneurysm clipping versus coiling has a differential effect on the risk of troponin release and left ventricular (LV) dysfunction after SAH is unknown. It is hypothesized that aneurysm treatment does not affect the risk of developing cardiac injury and dysfunction. METHODS:The study included 172 consecutive SAH patients who underwent clipping (n = 109) or coiling (n = 63) aneurysm therapy. Hemodynamic data were collected, cardiac troponin I was measured, and echocardiography was performed on the 1st, 3rd, and 6th days after enrollment. A cardiac troponin I measurement of more than 1.0 &mgr;g/L was considered abnormal. For each echocardiographic examination, a blinded observer measured LV ejection fraction (abnormal if <50%) and quantified LV regional wall motion abnormalities. The incidence of cardiac outcomes in the treatment groups was compared using odds ratios (ORs). RESULTS:The coiled patients were older than the clipped patients (mean age, 59 ± 13 yr versus 53 ± 12 yr; t test, P < 0.001) and were more likely to have posterior aneurysms (33% versus 18%; &khgr;2 test, P = 0.019). There were no significant between-group differences in the risk of cardiac troponin I release (coil 21% versus clip 19%; OR = 0.89, P = 0.789), regional wall motion abnormalities (33% versus 28%; OR = 0.76, P = 0.422), or LV ejection fraction lower than 50% (16% versus 17%; OR = 1.06, P = 0.892). No patient died of cardiac causes (heart failure, myocardial infarction, or arrhythmia). CONCLUSION:Surgical and endovascular aneurysm therapies were associated with similar risks of cardiac injury and dysfunction after SAH. The presence of neurocardiogenic injury should not affect aneurysm treatment decisions.

Response to Letter Regarding Article by Banki et al, “Acute Neurocardiogenic Injury After Subarachnoid Hemorrhage”

We were very interested to read Dr Gnecchi-Ruscone’s comments regarding our article.1 Similar to stress cardiomyopathy (SC), elevated catecholamine levels are frequently observed after subarachnoid hemorrhage (SAH).2 In our series, the mean plasma epinephrine and norepinephrine levels were 129±102 pg/mL and 372±494 pg/mL, respectively.3 The majority of the levels are lower than those reported for SC, …