Novel robotic TCD ultrasound with bubbles versus standard care to detect right to left shunt: Study methods.

BACKGROUND AND PURPOSE: Right to left shunt (RLS), from patent foramen ovale (PFO) or elsewhere, is a recognized risk factor for stroke. Current standard of care for RLS diagnosis includes transthoracic echocardiography (TTE) which is insensitive, transesophageal echocardiography (TEE) which is invasive, and transcranial Doppler (TCD) which has excellent sensitivity and specificity for RLS but is heavily operator dependent and expertise is scarce. The purpose of this study was to evaluate the RLS detection rate of a novel robotic-assisted TCD (ra-TCD) to standard of care diagnostic techniques, including TTE, TEE, and TCD. METHODS: This is a multicenter, prospective, single-arm, nonsignificant risk device study of ra-TCD versus TTE for RLS diagnosis in adult patients who present with neurological signs and symptoms that include embolic stroke or transient ischemic attack on the differential diagnosis. Up to 150 subjects will be enrolled at up to seven centers considering the prevalence of PFO, suboptimal transtemporal windows, and potential dropouts. Enrolled patients will undergo ra-TCD supine and at 45° in a manner otherwise in line with standard of care TCD bubble technique. The enrolled patients will have undergone TTE, and optionally standard TCD and TEE, per usual care. RESULTS: The primary efficacy endpoint is percent detection of RLS by ra-TCD compared against TTE. The primary safety endpoint is the incidence of device-related serious adverse events. CONCLUSIONS: This is the first multicenter, prospective study evaluating the accuracy, feasibility, and safety of novel ra-TCD for the diagnosis of RLS as compared to standard of care diagnostics.

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices.

BACKGROUND AND PURPOSE: Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). METHODS: From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. RESULTS: We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values. CONCLUSION: TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.

Cerebral Pulsatility Index Is Elevated in Patients with Elevated Right Atrial Pressure.

BACKGROUND AND PURPOSE: Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure. METHODS: We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure. RESULTS: There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P < .0001). This finding was consistent in sensitivity analysis that compared right and left hemispheric CPI from patients with both elevated and normal right atrial pressure. CONCLUSION: Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations.

Paradoxical cerebrovascular hemodynamic changes with nicardipine.

OBJECTIVE Intravenous nicardipine is commonly used for blood pressure reduction in patients with acute stroke. However, few studies have described its effects on cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform analysis and pulsatility index (PI). In this study, the authors report examples of a consistent but paradoxical finding associated with nicardipine that suggests intracranial vasoconstriction, contrary to what is expected from a vasodilator. METHODS The data presented are from a convenience sample of patients who underwent TCD monitoring before, after, or during nicardipine administration. In each case, TCD waveform morphologies and PIs were compared. RESULTS The TCD waveforms during nicardipine infusion are characterized by a prominent systolic peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were significantly elevated in patients who were on nicardipine (p < 0.001). This finding was not evident when patients were not on nicardipine. CONCLUSIONS This study provides the first evidence of paradoxical intracranial vasoconstriction associated with intravenous nicardipine. In the authors' experience, this finding is consistently encountered in the vast majority of patients who are treated with intravenous nicardipine, and is contradictory to what is expected from a vasodilator. Future studies are needed to confirm this finding in larger populations and diverse clinical settings and to examine mechanisms that explain this phenomenon.

Transcranial Doppler Changes in Patients Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND: Transcranial Doppler (TCD) has significant implications for neurovascular assessment in patients being treated with venoarterial-extracorporeal membrane oxygenation (VA-ECMO). However, there have been no studies demonstrating the changes in pulsatility indices (PIs) seen in these patients. Nonpulsatile waveforms are seen during on-pump coronary artery bypass graft, but low or low-normal PIs have never been reported. It is important to be aware of these changes, as they can be misinterpreted as cerebral vasodilation, vasoconstriction, increased intracranial pressures (ICPs), or cerebral circulatory arrest. METHODS: Data from 11 TCDs from 8 patients on VA-ECMO in the Cedars Sinai Medical Center Cardiac Surgical Intensive Care Unit were reviewed. Mean pulsatility indices were calculated for each patient using Gosling's PI formula. The values obtained were correlated with ejection fraction (EF) values obtained from a transthoracic or transesophageal echocardiogram. RESULTS: PIs were globally low or absent in all 11 TCDs. In 3 patients, TCDs were performed at the initiation and conclusion of the VA-ECMO cannulation. The PI values for these TCDs correlated directly with changes in EFs. Also, an abrupt rise in PI to normal value was seen with the placement of a total artificial heart and the return of pulsatile circulation. CONCLUSIONS: We demonstrate that PIs on TCDs in patients treated with VA-ECMO are either low or cannot be calculated depending on the severity of myocardial suppression, and should not be mistaken for cerebral vasodilation or cerebral circulatory arrest. Moreover, rising PIs in these patients can represent improving cardiac function and should not be confused with elevated ICPs.

Cerebral blood flow velocity and vasomotor reactivity during autonomic challenges in heart failure.

BACKGROUND: Significant alterations in autonomic nervous system (ANS) function, vasomotor reactivity, and cerebral blood flow may develop from damage to brain ANS regulatory areas in heart failure (HF). This preferentially right-sided injury occurs largely in autonomic structures perfused by the middle cerebral artery. Indications of altered, asymmetrical perfusion raise the potential for further neural damage. OBJECTIVE: To determine whether the extent of middle cerebral artery blood flow velocity and vasomotor reactivity is altered on one side of the brain over the other in HF versus control subjects, three ANS challenges were administered-each challenge recruited ANS regulatory areas potentially injured in HF. METHODS: Transcranial Doppler ultrasonography was used to measure cerebral blood flow velocity and vasomotor reactivity in 40 HF (mean age = 52.7 years, SD = 7.5; 27 men; left ventricular ejection fraction = 26.8, SD = 8.3) and 42 control subjects (mean age = 48.3 years, SD = 6.0; 22 men) during 5% CO2 and hyperventilation, Valsalva, and orthostatic (upper body tilt) challenges. RESULTS: Lower cerebral blood flow velocity and abnormal vasomotor reactivity (p < .01) were noted in HF middle cerebral arteries during all challenges. More right-sided flow velocity reductions appeared in HF, with laterality differences noted during CO2 and orthostatic (p < .05), but not Valsalva challenges. DISCUSSION: Diminished cerebral blood flow velocity and altered vasomotor reactivity were associated with HF, changes being preferentially on the right side; the asymmetry was more pronounced during CO2 and orthostatic challenges. The impaired blood flow regulation may contribute to the lateralized brain pathology in ANS areas, undermining autonomic control in HF.