Aortic valve calcification volumes and chronic brain infarctions in patients undergoing transcatheter aortic valve implantation

Chronic silent brain infarctions, detected as new white matter hyperintensities on magnetic resonance imaging (MRI) following transcatheter aortic valve implantation (TAVI), are associated with long-term cognitive deterioration. This is the first study to investigate to which extent the calcification volume of the native aortic valve (AV) measured with cardiac computed tomography angiography (CTA) predicts the increase in chronic white matter hyperintensity volume after TAVI. A total of 36 patients (79 ± 5 years, median EuroSCORE II 1.9%, Q1–Q3 1.5–3.4%) with severe AV stenosis underwent fluid attenuation inversion recovery (FLAIR) MRI < 24 h prior to TAVI and at 3 months follow-up for assessment of cerebral white matter hyperintensity volume (mL). Calcification volumes (mm3) of the AV, aortic arch, landing zone and left ventricle were measured on the CTA pre-TAVI. The largest calcification volumes were found in the AV (median 692 mm3) and aortic arch (median 633 mm3), with a large variation between patients (Q1–Q3 482–1297 mm3 and 213–1727 mm3, respectively). The white matter hyperintensity volume increased in 72% of the patients. In these patients the median volume increase was of 1.1 mL (Q1–Q3 0.3–4.6 mL), corresponding with a 27% increase from baseline (Q1–Q3 7–104%). The calcification volume in the AV predicted the increase of white matter hyperintensity volume (Δ%), with a 35% increase of white matter hyperintensity volume, per 100 mm3 of AV calcification volume (SE 8.5, p < 0.001). The calcification volumes in the aortic arch, landing zone and left ventricle were not associated with the increase in white matter hyperintensity volume. In 72% of the patients new chronic white matter hyperintensities developed 3 months after TAVI, with a median increase of 27%. A higher calcification volume in the AV was associated with a larger increase in the white matter hyperintensity volume. These findings show the potential for automated AV calcium screening as an imaging biomarker to predict chronic silent brain infarctions

Arterial pressure variations as parameters of brain perfusion in response to central blood volume depletion and repletion

Rationale: A critical reduction in central blood volume (CBV) is often characterized by hemodynamic instability. Restoration of a volume deficit may be established by goal-directed fluid therapy guided by respiration-related variation in systolic- and pulse pressure (SPV and PPV). Stroke volume index (SVI) serves as a surrogate end-point of a fluid challenge but tissue perfusion itself has not been addressed. Objective: To delineate the relationship between arterial pressure variations, SVI and regional brain perfusion during CBV depletion and repletion in spontaneously breathing volunteers. Methods: This study quantified in 14 healthy subjects (11 male) the effects of CBV depletion [by 30 and 70 degrees passive head-up tilt (HUT)] and a fluid challenge (by tilt back) on CBV (thoracic admittance), mean middle cerebral artery (MCA) blood flow velocity (V-mean), SVI, cardiac index (Cl), PPV, and SPV. Results: PPV (103 +/- 89%, p = 15% reduction in MCAV(mean) and SVI with comparable sensitivity (67/67% vs. 63/68%, respectively) and specificity (89/94 vs. 89/94%, respectively). A rapid fluid challenge by tilt-back restored all parameters to baseline values within 1 min. Conclusion: In spontaneously breathing subjects, a reduction in MCAVmean was related to an increase in PPV and SPV during graded CBV depletion and repletion. Specifically, PPV and SPV predicted changes in both SVI and MCAV(mean) comparable sensitivity and specificity, however the predictive value is limited in spontaneously breathing subject

Arterial Pressure Variation as a Biomarker of Preload Dependency in Spontaneously Breathing Subjects - A Proof of Principle.

Pulse (PPV) and systolic pressure variation (SPV) quantify variations in arterial pressure related to heart-lung interactions and have been introduced as biomarkers of preload dependency to guide fluid treatment in mechanically ventilated patients. However, respiratory intra-thoracic pressure changes during spontaneous breathing are considered too small to affect preload and stroke volume sufficiently for the detection by PPV and/or SPV. This study addressed the effects of paced breathing and/or an external respiratory resistance on PPV and SPV in detecting preload dependency in spontaneously breathing subjects.In 10 healthy subjects, hemodynamic and respiratory parameters were evaluated during progressive central hypovolemia (head-up tilt). Breathing conditions were varied by manipulating breathing frequency and respiratory resistance. Subjects responding with a reduction in stroke volume index ≥15% were classified as having developed preload dependency. The ability for PPV and SPV to predict preload dependency was expressed by the area under the ROC curve (AUC).A breathing frequency at 6/min increased the PPV (16±5% vs. 10±3%, p<0.001) and SPV (9±3% vs. 5±2%, p<0.001) which was further enhanced by an expiratory resistance (PPV: 19±3%, p = 0.025 and SPV: 10±2%, p = 0.047). These respiratory modifications, compared to free breathing, enhanced the predictive value of PPV with higher accuracy (AUC: 0.92 vs. 0.46).Under conditions of progressive central hypovolemia, the application of an external respiratory resistance at a breathing frequency of 6/min enhanced PPV and SPV and is worth further study for detection of preload dependency from arterial pressure variations in non-ventilated subjects

Experimental protocol.

<p>After instrumentation the measurements started with the subject in the supine position, followed by 30 and 70° head-up tilt with a 5 minute adjustment period in between (layer 1). Each test run encompasses three breathing conditions (layer 2, here only shown for the supine position) with and without an respiratory resistance (layer 3, here only shown for free breathing). The order of the breathing frequency and use of a respiratory resistance was randomized.</p

ROC curve plots of pulse (PPV) and systolic pressure variation (SPV) during two different breathing conditions.

<p>6/min paced breathing against an expiratory resistance significantly increased the area under the ROC curve of PPV (p = 0.047).</p

Illustration of the effect of 6/min paced breathing against an expiratory resistance for a single recumbent subject.

<p>AWF, airway flow; AWP, airway pressure; respCO₂, respiratory CO₂ partial pressure.</p

Abnormal haemodynamic postural response in patients with chronic heart failure

Aim The objective was to evaluate in treated heart failure (HF) patients whether multidrug therapy interferes with the cardiovascular autonomic response to postural stress. Methods and results Blood pressure (BP; Finapres), heart rate (HR), stroke volume, and total peripheral resistance (TPR) responses to standing up were measured in 33 HF patients and 10 healthy age-matched controls. Ten hypertensive (HT) patients treated with a similar combination of drugs but without heart failure served as reference subjects to account for use of medication. Frequency domain measures of HR and BP variability were calculated as correlates of cardiovascular autonomic function. Postural hypotension was found in 16 out of 33 HF patients independently from New York Heart Association functional class. In HF patients vs. HT patients and healthy controls the haemodynamic postural response was abnormal with a large initial BP fall and a slackened reflex increase in TPR resulting in inadequate BP recovery. HR and BP variability were normal in HT patients and healthy controls but attenuated in HF patients. The magnitude of the postural HR, stroke volume, and TPR responses as well as HR and BP variability was inversely related to the New York Heart Association class. Conclusions In HF patients, the autonomic vasomotor response to postural stress is abnormal, more pronounced with increasing disease severity, and frequently associated with overt postural hypotension. These phenomena appear related to the cardiac condition rather than treatmen

The cerebrovascular response to lower-body negative pressure vs. head-up tilt

Lower-body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (-50 mmHg) vs. head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler-determined cerebral blood flow velocity (CBFv) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT, leading to an ~15% difference in CPP between LBNP and HUT (P ≤ 0.020). Mean CBFv initially decreased similarly in response to LBNP and for HUT, but, from minute 3 on, the decline became ~50% smaller (P ≤ 0.029) during LBNP. The reduction in end-tidal Pco2 partial pressure (PetCO2 ) was comparable but with an earlier return toward baseline values in response to LBNP but not during HUT (P = 0.008). We consider the larger decrease in CBFv during HUT vs. LBNP attributable to the pronounced reduction in PetCO2 and to gravitational influences on CPP, and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality.NEW & NOTEWORTHY Lower-body negative pressure (LBNP) has the potential to serve as a MRI-compatible surrogate of orthostatic stress but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco2 together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as MRI-compatible alternative to orthostatic stres

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) value