ICP versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity

Objective: To explore the relationship between various autoregulatory indices in order to determine which approximate small-vessel/microvascular autoregulatory capacity most accurately. Methods: Utilizing a retrospective cohort of traumatic brain injury (TBI) patients (N=41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived (pressure reactivity index (PRx) – correlation between ICP and mean arterial pressure (MAP), PAx – correlation between pulse amplitude of ICP (AMP) and MAP, RAC – correlation between AMP and cerebral perfusion pressure (CPP)), B. TCD derived (Mx – correlation between mean flow velocity (FVm) and CPP, Mx_a – correlation betrween FVm and MAP, Sx – correlation between systolic flow velocity (FVs) and CPP, Sx_a – correlation between FVs and MAP, Dx – correlation between diastolic flow index (FVd) and CPP, Dx_a – correlation between FVd and MAP), and LDF derived (Lx – correlation between LDF cerebral blood flow (CBF) and CPP, Lx_a – correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). Results: LDF based autoregulatory index (Lx) was most associated with TCD based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC and KMCA. Lx was only remotely associated with ICP based indices (PRx, PAx, RAC). TCD based Sx/Sx_a were more closely associated with ICP derived PRx, PAx and RAC. This indicates that vascular derived indices of autoregulatory capacity (ie. TCD and LDF based) co-vary, with Sx/Sx_a being the exception. Whereas, indices of cerebrovascular reactivity derived from pulsatile CBV (ie. ICP indices) appear to not be closely related to those of vascular origin. Conclusions: Transcranial Doppler Mx is the most closely associated with LDF based Lx/Lx_a. Both Sx/Sx-a and the ICP derived indices appear to be dissociated with LDF based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/microvascular cerebrovascular reactivity. Sx/Sx_a co-cluster/co-vary with ICP derived indices, as seen in our previous work.This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. These studies were supported by National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150) MC is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1790). JD is supported by a Woolf Fisher Scholarship (NZ)

From hypertrophic cardiomyopathy centers to inherited cardiovascular disease centers in Europe. A small or a major step? A position paper from the Nucleus of the Working Group on Myocardial and Pericardial Diseases of the Portuguese Society of Cardiology.

The prevalence, complexity, clinical importance, heterogeneity and unpredictability of inherited cardiovascular diseases make the development of inherited cardiovascular disease centers an inevitability, with the ultimate goal of reducing the morbidity and mortality associated with these conditions. An inherited cardiovascular disease center may be seen as a subunit of a cardiology department, with health professionals specializing in these types of disorders, organized to provide excellence in all related areas, including diagnosis, treatment, followup, prevention, risk stratification and prognosis. Among its objectives are the development of action protocols and the creation of databases that enable patients to be included in national and international research networks. To achieve these objectives these centers should include functional units of clinical and basic sciences, research, training and education, acting in harmony in a holistic approach to patients and their families. As most experience on inherited cardiovascular diseases is based on hypertrophic cardiomyopathy and on "hypertrophic cardiomyopathy centers", these centers represent an excellent opportunity to learn how to set up inherited cardiovascular disease centers. European centers will differ from country to country, reflecting the heterogeneity of national health systems, but will share a common core, presented in this document. Though we are aware that this ambitious project is not at all easy and may be difficult to implement in its entirety--in fact we consider it a major step--our position is that all the efforts to achieve it are worthwhile, considering that the main goal will always be the well-being of those affected by these particular disorders

Transcranial Doppler Monitoring of Intracranial Pressure Plateau Waves

$\textbf{BACKGROUND}$: Transcranial Doppler (TCD) has been used to estimate ICP noninvasively (nICP); however, its accuracy varies depending on different types of intracranial hypertension. Given the high specificity of TCD to detect cerebrovascular events, this study aimed to compare four TCD-based nICP methods during plateau waves of ICP. $\textbf{METHODS}$: A total of 36 plateau waves were identified in 27 patients (traumatic brain injury) with TCD, ICP, and ABP simultaneous recordings. The nICP methods were based on: (1) interaction between flow velocity (FV) and ABP using a "black-box" mathematical model (\textit{nICP_BB}); (2) diastolic FV (\textit{nICP_FV}$_{d}$); (3) critical closing pressure (\textit{nICP_CrCP}), and (4) pulsatility index (\textit{nICP_PI}). Analyses focused on relative changes in time domain between ICP and noninvasive estimators during plateau waves and the magnitude of changes ($\textit{∆}$ between baseline and plateau) in real ICP and its estimators. A ROC analysis for an ICP threshold of 35 mmHg was performed. $\textbf{RESULTS}$: In time domain, \textit{nICP_PI, nICP_BB,} and \textit{nICP_CrCP} presented similar correlations: 0.80 ± 0.24, 0.78 ± 0.15, and 0.78 ± 0.30, respectively. \textit{nICP_FV}$_{d}$ presented a weaker correlation (R = 0.62 ± 0.46). Correlations between ∆ICP and ∆nICP were better represented by \textit{nICP_CrCP} and BB, R = 0.48, 0.44 (p < 0.05), respectively. \textit{nICP_FV}$_{d}$ and $\textit{PI}$ presented nonsignificant $\textit{∆}$ correlations. ROC analysis showed moderate to good areas under the curve for all methods: \textit{nICP_BB}, 0.82; \textit{nICP_FV}$_{d}$, 0.77; \textit{nICP_CrCP}, 0.79; and \textit{nICP_PI}, 0.81. $\textbf{CONCLUSIONS}$: Changes of ICP in time domain during plateau waves were replicated by nICP methods with strong correlations. In addition, the methods presented high performance for detection of intracranial hypertension. However, absolute accuracy for noninvasive ICP assessment using TCD is still low and requires further improvement

The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results

INTRODUCTION: We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal. METHODS: A direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected. RESULTS: A total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31% were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular mortality 0.65%/year. The incidence of heart failure-related death was 0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death 0.04%/year. Heart failure-related death plus heart transplantation occurred in 0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year. CONCLUSIONS: Contemporary HCM in Portugal is characterized by relatively advanced age at diagnosis, and a high proportion of invasive treatment of obstructive forms. Long-term mortality is low; heart failure is the most common cause of death followed by sudden cardiac death. However, the burden of morbidity remains considerable, emphasizing the need for disease-specific treatments that impact the natural history of the disease.info:eu-repo/semantics/publishedVersio

O Índice de Resistência Microcirculação Para o Estudo Invasivo da Microcirculação Coronária. Descrição e Validação de um Modelo Animal

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status

The Association Between Peri-Hemorrhagic Metabolites and Cerebral Hemodynamics in Comatose Patients With Spontaneous Intracerebral Hemorrhage: An International Multicenter Pilot Study Analysis.

Background and Objective: Cerebral microdialysis (CMD) enables monitoring brain tissue metabolism and risk factors for secondary brain injury such as an imbalance of consumption, altered utilization, and delivery of oxygen and glucose, frequently present following spontaneous intracerebral hemorrhage (SICH). The aim of this study was to evaluate the relationship between lactate/pyruvate ratio (LPR) with hemodynamic variables [mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebrovascular pressure reactivity (PRx)] and metabolic variables (glutamate, glucose, and glycerol), within the cerebral peri-hemorrhagic region, with the hypothesis that there may be an association between these variables, leading to a worsening of outcome in comatose SICH patients. Methods: This is an international multicenter cohort study regarding a retrospective dataset analysis of non-consecutive comatose patients with supratentorial SICH undergoing invasive multimodality neuromonitoring admitted to neurocritical care units pertaining to three different centers. Patients with SICH were included if they had an indication for invasive ICP and CMD monitoring, were &gt;18 years of age, and had a Glasgow Coma Scale (GCS) score of ≤8. Results: Twenty-two patients were included in the analysis. A total monitoring time of 1,558 h was analyzed, with a mean (SD) monitoring time of 70.72 h (66.25) per patient. Moreover, 21 out of the 22 patients (95%) had disturbed cerebrovascular autoregulation during the observation period. When considering a dichotomized LPR for a threshold level of 25 or 40, there was a statistically significant difference in all the measured variables (PRx, glucose, glutamate), but not glycerol. When dichotomized PRx was considered as the dependent variable, only LPR was related to autoregulation. A lower PRx was associated with a higher survival [27.9% (23.1%) vs. 56.0% (31.3%), p = 0.03]. Conclusions: According to our results, disturbed autoregulation in comatose SICH patients is common. It is correlated to deranged metabolites within the peri-hemorrhagic region of the clot and is also associated with poor outcome

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Trust Scholarship. BCTC is supported by CNPQ (Research Project 203792/2014-9). DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00701-015-2661-

The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results

INTRODUCTION: We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal. METHODS: A direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected. RESULTS: A total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31% were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular mortality 0.65%/year. The incidence of heart failure-related death was 0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death 0.04%/year. Heart failure-related death plus heart transplantation occurred in 0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year. CONCLUSIONS: Contemporary HCM in Portugal is characterized by relatively advanced age at diagnosis, and a high proportion of invasive treatment of obstructive forms. Long-term mortality is low; heart failure is the most common cause of death followed by sudden cardiac death. However, the burden of morbidity remains considerable, emphasizing the need for disease-specific treatments that impact the natural history of the disease

Diagnosis and treatment of acute myocarditis in Portugal. Data from the national multicenter registry on myocarditis

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.Introduction: The diagnosis of acute myocarditis (aMyo) needs a high level of suspicion. Cardiac magnetic resonance (CMR) may contribute to the diagnosis; but endomyocardial biopsy (EMB) is considered the gold standard, although used infrequently worldwide. Short-term course, albeit unpredictable is usually benign and treatment is mainly supportive. Objectives: To assess the usual care attitudes regarding hospitalized patients (pts) with a diagnosis of aMyo in Portugal, report patient's clinical profiles and current therapeutic approaches, and assess the relevance of CMR to eventual changes in management and/or therapeutic decisions. Methods: Prospective nationwide survey of admitted aMyo pts during a 2-year period (25.04.13–15). Electronic CRFs were completed with admission/discharge data, diagnostic tests, treatments and open-ended questions to evaluate physician's opinions and conclusions. Results: 248 pts from 18 centers were included, 98% caucasian, 35±14 (18–84) years old, 83% male. A recent infectious disease was detected in 57.5% (upper respiratory tract in 71.2%) and 23% had been previously treated with antibiotics. On admission, presentation included angina-like thoracic pain (96%), non-CV symptoms- 58.4% (fever-71%, respiratory- 52.8%, GI- 28.1%), heart failure (HF)- 5.4% and cardiogenic shock- 0.8%; abnormal ECG - 82% (mostly ST elevation-78.5%); increased troponin levels in 95%; echo (in 94%pts) showed left ventricular dilatation (LVD) - 5.7%, segmental LV wall abnormalities (segmAbn) - 34%, reduced LV ejection fraction (RLVEF) - 21% and pericardial effusion (PE) - 11.7%. CMR (in 57%pts), didn't change the management in 70% of cases. Coronary angiography (in 40%) revealed significant CAD in 7.4%. EMB was diagnostic in the 2 pts in which was performed (due to severe progressive HF). Multiple viral serologies (in 32.4% pts) were conclusive in only 0.5%. Most pts were treated with NSAIDs, 39% received ACEi or ARB, 36% a beta-blocker (BB) and 8.4% diuretics; 3.4% needed inotropes. Only 1 death occurred (shock). At discharge, an abnormal ECG persisted in 64.4% of pts; echo (in 50.4%) showed LVD in 6%, segmAbn in 24.6%, RLVEF in 14.6% and PE in 10.2%. Most pts (88.2%) were discharged on NSAIDs, 37.6% on ACEi or ARB, 30.36% on BB, and 6.47% on diuretics. Final diagnosis was aMyo in 54.4% (probable/possible in 96.9% and definitive in only 3.1%) and myopericarditis in 45.6%. Diagnostic criteria were “clinical” in 96.4%, supported by lab results in 87.7% and ECG in 68.8%. Echo or CMR contribution in supporting “clinical diagnosis”, was 38.3% and 48.6% respectively. Disease course was in most cases “mild” (87%). Conclusions: Echo and CMR were performed in most pts with aMyo but diagnosis remained mostly “clinical” according to treating physicians. EMB was very rarely performed. Treatment was largely empirical but an “overuse” of CV drugs and NSAIDs was observed.info:eu-repo/semantics/publishedVersio