Search

BACKGROUND Hypertension (HTN) has the greatest population-attributable risk for aortic dissection and is highly prevalent among patients with thoracic aortic aneurysms (TAAs). Although HTN is diagnosed based on brachial blood pressure (bBP), central HTN (central systolic blood pressure [cSBP] ≥130 mm Hg) is of interest as it better reflects blood pressure (BP) in the aorta. We aimed to (i) evaluate the prevalence of central HTN among TAA patients without a diagnosis of HTN, and (ii) assess associations of bBP vs. central blood pressure (cBP) with aneurysm size and growth. METHODS One hundred and five unoperated subjects with TAAs were recruited. With validated methodology, cBP was assessed with applanation tonometry. Aneurysm size was assessed at baseline and follow-up using imaging modalities. Aneurysm growth rate was calculated in mm/year. Multivariable linear regression adjusted for potential confounders assessed associations of bBP and cBP with aneurysm size and growth. RESULTS Seventy-seven percent of participants were men and 49% carried a diagnosis of HTN. Among participants without diagnosis of HTN, 15% had central HTN despite normal bBP (“occult central HTN”). In these patients, higher central systolic BP (cSBP) and central pulse pressure (cPP) were independently associated with larger aneurysm size (β ± SE = 0.28 ± 0.11, P = 0.014 and cPP = 0.30 ± 0.11, P = 0.010, respectively) and future aneurysm growth (β ± SE = 0.022 ± 0.008, P = 0.013 and 0.024 ± 0.009, P = 0.008, respectively) while bBP was not (P > 0.05). CONCLUSIONS In patients with TAAs without a diagnosis of HTN, central HTN is prevalent, and higher cBP is associated with larger aneurysms and faster aneurysm growth.

Background Heart failure (HF) is the leading cause of death in adult patients with congenital heart disease (ACHD). No risk prediction model exists for HF hospitalization (HFH) for ACHD patients. We aimed to develop a clinically relevant one-year risk prediction system to identify ACHD patients at high risk for HFH. Methods Data source was the Quebec CHD Database. A retrospective cohort including all ACHD patients aged 18–64 (1995–2010) was constructed for assessing the cumulative risk of HFH adjusting for competing risk of death. To identify one-year predictors of incident HFH, multivariable logistic regressions were employed to a nested case-control sample of all ACHD patients aged 18–64 in 2009. The final model was used to create a risk score system based on adjusted odds ratios. Results The cohort included 29,991 ACHD patients followed for 648,457 person-years. The cumulative HFH risk by age 65 was 12.58%. The case-control sample comprised 26,420 subjects, of whom 189 had HFHs. Significant one-year predictors were age ≥ 50, male sex, CHD lesion severity, recent 12-month HFH history, pulmonary arterial hypertension, chronic kidney disease, coronary artery disease, systemic arterial hypertension, and diabetes mellitus. The created risk score ranged from 0 to 19. The corresponding HFH risk rose rapidly beyond a score of 8. The risk scoring system demonstrated excellent prediction performance. Conclusions One eighth of ACHD population experienced HFH before age 65. Age, sex, CHD lesion severity, recent 12-month HFH history, and comorbidities constructed a risk prediction model that successfully identified patients at high risk for HFH.

Background Tricuspid regurgitation (TR) is common among adults with corrected tetralogy of Fallot (TOF) or pulmonary stenosis (PS) referred for pulmonary valve replacement (PVR). Yet, combined valve surgery remains controversial. Objectives This study sought to evaluate the impact of concomitant tricuspid valve intervention (TVI) on post-operative TR, length of hospital stay, and on a composite endpoint consisting of 7 early adverse events (death, reintervention, cardiac electronic device implantation, infection, thromboembolic event, hemodialysis, and readmission). Methods The national Canadian cohort enrolled 542 patients with TOF or PS and mild to severe TR who underwent isolated PVR (66.8%) or PVR+TVI (33.2%). Outcomes were abstracted from charts and compared between groups using multivariable logistic and negative binomial regression. Results Median age at reintervention was 35.3 years. Regardless of surgery type, TR decreased by at least 1 echocardiographic grade in 35.4%, 66.9%, and 92.8% of patients with pre-operative mild, moderate, and severe insufficiency. In multivariable analyses, PVR+TVI was associated with an additional 2.3-fold reduction in TR grade (odds ratio [OR]: 0.44; 95% confidence interval [CI]: 0.25 to 0.77) without an increase in early adverse events (OR: 0.85; 95% CI: 0.46 to 1.57) or hospitalization time (incidence rate ratio: 1.17; 95% CI: 0.93 to 1.46). Pre-operative TR severity and presence of transvalvular leads independently predicted post-operative TR. In contrast, early adverse events were strongly associated with atrial tachyarrhythmia, extracardiac arteriopathy, and a high body mass index. Conclusions In patients with TOF or PS and significant TR, concomitant TVI is safe and results in better early tricuspid valve competence than isolated PVR.

Background Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course. Methods We performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients’ prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27–3.62; HR 3.42, 95%CI 2.72–4.31; HR 2.79, 95%CI 2.32–3.35), and Cluster 1 (HR 1.88, 95%CI 1.48–2.38; HR 2.50, 95%CI 1.98–3.15; HR 2.09, 95%CI 1.74–2.51) reported a higher risk for the three outcomes respectively. Conclusions In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.

Thoracic aortic aneurysm (TAA) is a highly morbid disease. We have previously shown that baseline hemodynamic measures reflecting aortic function are associated with future TAA expansion. However, whether serial arterial hemodynamic assessment further improves TAA growth assessment remains unknown. Therefore, we aimed to compare single vs serial arterial hemodynamic assessments in the evaluation of future TAA growth.Eighty-six unoperated participants with TAA underwent noninvasive arterial hemodynamic assessment using arterial tonometry and echocardiography at baseline and after 1 year. Aortic diameter was measured serially with the use of standard imaging modalities. Stepwise multivariable linear regression was used to assess associations of baseline and 1-year change (Δ) in arterial hemodynamic measures with TAA growth.Mean age was 62.7 ± 11.0 years; 79% were male. Mean aneurysm growth was 0.48 ± 0.54 mm/year after a follow-up of 2.96 ± 1.03 years. Yearly changes in arterial hemodynamic measures ranged from -3.2% to +4.2%. Linear regression results showed that while baseline arterial hemodynamic measures were independently associated with aneurysm growth (carotid-femoral pulse wave velocity: β ± SE = 0.038 ± 0.013; aortic characteristic impedance: β ± SE = 0.002 ± 0.001; proximal aortic compliance: β ± SE = -0.011 ± 0.006; forward pressure wave amplitude: β ± SE 0.009 ± 0.002; reflected pressure wave amplitude: β ± SE = 0.017 ± 0.006; P0.05 for each), the 1-year Δ in these measures did not incrementally add to aneurysm growth assessment (P0.05 for each Δ).Although baseline measures of aortic function independently predict TAA expansion, 1-year changes in these measures do not improve this prediction. Thus, for TAA risk assessment purposes, a baseline assessment of aortic function may suffice, which simplifies its use for potential predictive algorithms.

BACKGROUND Mitral annular calcification (MAC) is a common finding, but the natural history and risk for developing calcific mitral valve disease (CMVD) have been poorly defined. We sought to evaluate the progression rate of MAC and of the development of CMVD. METHODS AND RESULTS Patients with at least mild MAC and paired echocardiograms at least one year apart between 2005 and 2019 were included. Progression rates from mild/moderate MAC to severe MAC and to CMVD (defined as severe MAC and significant mitral stenosis and/or regurgitation) were assessed, along with potential associations with sex and aortic valve stenosis (AS) progression. A total of 11,605 patients (73±10 years, 51% male) with MAC (78% mild, 17% moderate, 5% severe) were included and had a follow up echocardiogram at 4.2±2.7 years. In patients with mild/moderate MAC on their initial echocardiogram, the incidence of severe MAC at 10 years was 33%. The incidence was higher in females than in males (41% vs. 24%, P CONCLUSION In this large patient cohort with MAC, progression to severe MAC is common and frequently results in CMVD. Female sex was associated with higher progression rates and an association between MAC and AS progression was observed. MAC and CMVD are expected to dramatically increase as the population ages and there is an urgent need to better understand the pathophysiology of MAC in order to develop effective preventative medical therapies.

Thoracic aortic aneurysm is a disease associated with high morbidity and mortality. Clinically useful strategies for medical management of thoracic aortic aneurysm are critically needed. To address this need, we sought to determine the role of aortic stiffness and pulsatile arterial load on future aneurysm expansion. One hundred five consecutive, unoperated subjects with thoracic aortic aneurysm were recruited and prospectively followed. By combining arterial tonometry with echocardiography, we estimated measures of aortic stiffness, central blood pressure, steady, and pulsatile arterial load at baseline. Aneurysm size was measured at baseline and follow-up with imaging; growth was calculated in mm/y. Stepwise multivariable linear regression assessed associations of arterial stiffness and load measures with aneurysm growth after adjusting for potential confounders. Mean±SD age, baseline aneurysm size, and follow-up time were 62.6±11.4 years, 46.24±3.84 mm, and 2.92±1.01 years, respectively. Aneurysm growth rate was 0.43±0.37 mm/y. After correcting for multiple comparisons, higher central systolic (β±SE: 0.026±0.009, P =0.007), and pulse pressures (β±SE: 0.032±0.009, P =0.0002), carotid-femoral pulse wave velocity (β±SE: 0.032±0.011, P =0.005), amplitudes of the forward (β±SE: 0.044±0.012, P =0.0003) and reflected (β±SE: 0.060±0.020, P =0.003) pressure waves, and lower total arterial compliance (β±SE: −0.086±0.032, P =0.009) were independently associated with future aneurysm growth. Measures of aortic stiffness and pulsatile hemodynamics are independently associated with future thoracic aortic aneurysm growth and provide novel insights into disease activity. Our findings highlight the role of central hemodynamic assessment to tailor novel risk assessment and therapeutic strategies to patients with thoracic aortic aneurysm.

Aims Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) Methods and results In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P Conclusion In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H

Background Thoracic aortic aneurysm (TAA) is a deadly disease in critical need of novel strategies for risk assessment and medical management. To address this need, we have previously shown that directly measured carotid-femoral pulse wave velocity (cfPWV), a marker of aortic stiffness and health, independently predicts future TAA expansion. Since aortic pulse wave velocity can be estimated from age and mean arterial pressure (MAP), in the present study we sought to determine whether estimated aortic pulse wave velocity (e-aPWV) also predicts TAA expansion. Methods One hundred and five consecutive, unoperated subjects with TAA were recruited. e-aPWV was estimated from validated equations based on age and MAP. cfPWV was measured with arterial tonometry according to guidelines. TAA size was measured at baseline and at the latest follow-up using available imaging modalities according to guidelines. Stepwise multivariable linear regression (P≤0.25 to enter, P≤0.10 to stay in the model) assessed independent associations of e-aPWV and cfPWV with future TAA growth. Variables considered in the models were: age, sex, BSA, MAP, TAA etiology and location, baseline TAA size, follow-up time, imaging modality, history of hypertension, diabetes and smoking. Results Seventy eight percent of subjects were men. Mean±SD age, baseline aneurysm size and follow-up time were 62.6±11.4 years, 46.2±3.8 mm and 3.0±1.0 years, respectively. e-aPWV and cfPWV were moderately correlated (Pearson's correlation coefficient = 0.61). Results of the linear regression analyses showed that both measured (cfPWV) and estimated (e-aPWV) independently predicted future TAA expansion (β±SE: 0.032±0.011, P=0.048 and 0.240±0.085, P=0.006, respectively). The base model's R-squared value of 0.39 was increased to 0.44 with addition of either cfPWV or e-aPWV to the model, confirming that each parameter of aortic stiffness enhances prediction of TAA growth. Conclusion Aortic stiffness is relevant for assessment of TAA disease activity. Similar to cfPWV, e-aPWV is also independently associated with future TAA expansion. Thus, e-aPWV represents a tool to improve TAA risk stratification that is simple, free of cost, and obviates the need for specialized equipment or dedicating training, which leads to excellent potential for widespread incorporation into clinical practice. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research

BACKGROUND: Increased aortic pulse wave velocity (PWV), a direct measure of arterial stiffness (AS) is an independent predictor of cardiovascular events (CVEs) in chronic kidney disease (CKD) patients. This study assessed the patterns of PWV among Cameroonian patients with CKD in whom that marker of early vascular aging has not been explored so far. METHODS: We enrolled 150 Black African patients (mean age: 52±15 years, 56.7% males) with CKD in a cross-sectional study conducted at Douala General Hospital, Douala, Cameroon. Sociodemographic, anthropometric and biologic variables, blood pressure (BP) and PWV were recorded in all participants. Estimated aortic PWV was measured using a Mobil-O-Graph automatic brachial oscillometric device. RESULTS: PWV increased with aging (P

Pygmies living in the Central African rainforest with a traditional hunter-gatherer lifestyle have a low incidence of cardiovascular diseases. Because of progressive loss of traditional habitat and ancestral lands, some Pygmies have migrated to urban areas and adopt specific Bantu lifestyles such as increased salt consumption and a sedentary way of life. We tested the hypothesis that migrant Pygmies could present with hemodynamic and metabolic characteristics different from those of traditional in-situ Pygmies and possibly closer to those of Bantu farmers.The study included 148 Pygmies (94 traditional and 54 migrants) and 164 Bantus. Peripheral and central hemodynamics, aortic pulse wave velocity (PWV), and augmentation index corrected for heart rate (AIx) were measured, as well as fasting lipid profile. Urinary sodium and potassium excretion was also measured on a morning spot.Compared to Bantus, Pygmies had lower height (even between men and women, but men were taller than women in the three groups), weight, waist and hip circumference, peripheral and central blood pressure, total, low-density lipoprotein, and high-density lipoprotein cholesterol and apolipoprotein B100 levels, sodium urinary excretion, and lower prevalence of the metabolic syndrome. By contrast, they had a higher waist-to-hip ratio, and higher triglycerides levels, as compared to Bantu farmers. PWV and AIx did not differ between Bantus and Pygmies. Compared to traditional in-situ Pygmies, migrant Pygmies were not taller when adjusted for sex, had lower brachial and central blood pressure, higher PWV (adjusted for mean arterial pressure, BMI, and sex), and higher apolipoprotein B100 levels. In the whole population, multivariable analysis revealed that PWV was independently associated with age, weight, height, mean arterial pressure, total cholesterol, and hip circumference, whereas AIx was independently related to age, sex, height, heart rate, diastolic blood pressure, and group (from Bantu farmers to Pygmies).Comparisons between Bantus and Pygmies, and between migrant Pygmies and traditional in-situ Pygmies, showed mixed results, with favorable and deleterious hemodynamic and metabolic characteristics in all groups. This could be due to increased contacts between these populations, which blunt the expected differences and because the beneficial effects of the hunter-gatherer subsistence mode of traditional in-situ Pygmies are counterbalanced by unhealthy behavioral habits.

Simple Summary High-risk soft tissue sarcomas (HR-STS) account for less than 1% of all malignancies in adults. Despite optimal local treatment, almost half of patients will die within five years of their diagnosis. Chemoresistance is a major responsible mechanism for treatment failure in advanced tumor stages. In contrast to other cancer types, molecular predictors of response to chemotherapy and survival have not been identified and put into clinical practice by now. We analyzed the predictive value of two molecules involved in the working and resistance mechanisms to doxorubicin, TOP2A and SIRT1, in a large cohort of locally advanced HR-STS who underwent a neoadjuvant anthracycline-based chemotherapy with a long-term follow-up. Our results show sarcoma subtype-specific patterns of TOP2A and SIRT1 expression. We demonstrate significant differences in overall survival according to the TOP2A and SIRT1 expression status. Both markers can be used as clinically significant predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy. Abstract Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.

Introduction Thoracic aortic aneurysm (TAA) is a clinically silent disease which can lead to significant morbidity when complicated by an acute aortic syndrome. Although TAA size is the only variable used in decision-making, it is an imperfect predictor of risk. Conversely, hemodynamic measures that reflect the aorta's function, such as aortic stiffness and pulsatile hemodynamics, may provide additional insights into risk of TAA expansion. Purpose We hypothesized that combining aortic size with measures of arterial function (stiffness and pulsatile hemodynamics) would improve prediction of TAA expansion, as compared to aortic size alone. Methods 105 unoperated participants with TAA were recruited between 2014 and 2017 and followed prospectively for ≥1 yr. TAA size was measured at enrolment and at the latest imaging study according to published consensus; TAA expansion was calculated as mm/year. Arterial function was non-invasively assessed at baseline with validated methods that integrate arterial tonometry with echocardiography. Multivariable linear regression assessed independent associations of baseline TAA size and each arterial function measure, initially separately and then in combination (by multiplying them when direction of association was the same, and dividing them when direction of association was opposite), with future TAA expansion. Standardized beta coefficients were calculated to allow direct comparisons. Models were adjusted for age, sex, body size, aneurysm location and etiology, type of imaging modality, follow-up time, mean arterial pressure, and history of hypertension, diabetes and smoking. Results Seventy-seven percent of participants were men, and the ratio of degenerative to heritable TAAs was 62/43. Mean ± SD age, baseline TAA size, and follow-up time were 62.8±11.3yrs, 46.3±3.9cm, and 2.2±0.7 years, respectively. Results of the multivariable linear regression models are summarized in the Table. While baseline TAA size and each arterial function measure were independently associated with TAA expansion, some of the arterial function measures were superior in predicting TAA growth (Table, left). In addition, combining aortic size and function further improved the prediction of TAA growth beyond each variable alone (Table, right). Conclusion(s) Combining aortic size with arterial function improved prediction of TAA expansion over any individual variable alone, independently of confounders. Assessing arterial function may confer a clinical advantage, when compared to current practice, in determining TAA disease activity and estimating one's TAA-related risk. Acknowledgement/Funding Canadian Institute of Health Research, Canadian Vascular Network, and Heart and Stroke Foundation of Canada

Background Bicuspid aortic valve ( BAV ) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm ( TAA ) is present in ≈50% of BAV patients, who also have an 8‐fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV . Methods and Results Twenty‐nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow‐up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (β± SE for carotid‐femoral pulse wave velocity: 0.30±0.13. P =0.03) and aortic characteristic impedance (β± SE : 0.46±0.18, P =0.02), as well as lower total arterial and proximal aortic compliance (β± SE : −0.44±0.21, P =0.05, and −0.63±0.16, P =0.001, respectively) were independently associated with faster aneurysm growth. Conclusions In patients with TAA due to BAV , measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV .

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have several advantages over VKAs that render them an attractive option for adults with congenital heart disease (CHD). Efficacy and safety data specific to the adult CHD population are emerging. Herein, we synthesize the growing literature regarding NOACs in adults with CHD and attempt to identify subgroups for which it appears reasonable to extrapolate data from populations without CHD. Small observational studies suggest that NOACs are safe and effective in selected adults with CHD. NOACs are contraindicated in patients with a mechanical valve, in those with mitral or tricuspid valve stenosis with enlarged and diseased atria, with or without a mitral or tricuspid bioprosthesis, and after recent cardiac surgery (< 3 months). There is currently insufficient evidence to recommend NOACs in patients with a Fontan circulation or cyanotic CHD. Growing literature supports the use of NOACs in patients without CHD who have various forms of valvular heart disease. Therefore, when an indication for oral anticoagulation is established, it appears reasonable to consider a NOAC instead of a VKA in adults with CHD lesions analogous to isolated mitral regurgitation, tricuspid regurgitation, or aortic regurgitation or stenosis. The NOAC agent selected and the prescribed dose should be tailored according to bleeding risk, body weight, renal function, and comedications, especially antiepileptic drugs. The decision to initiate a NOAC should be shared between the patient and care provider. Large-scale research studies are required to further assess safety and efficacy in selected patient subgroups.

Introduction: The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH). Methods: 124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated. Results: 122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (−25.8 ± 12 vs −21.2 ± 14 mm Hg, P

Drug-induced proarrhythmia is strongly focused on Torsade de Pointes (TdP), and QT prolongation is commonly used as a surrogate for TdP. This surrogate may be of limited value, as it produces false positives and false negatives. Cardiac electrophysiological parameters were obtained from monophasic action potentials recorded from Langendorff perfused female rabbit hearts. In 3939 experiments 179 VFs and 124 TdPs occurred during testing of various chemicals. TdP occurred with prolongation of action potential duration (APD), but also with shortening. Thus, APD/QT prolongation alone cannot predict TdP. Drug-induced abnormalities, associated with TdP or VF, were identified. The 11 most predictive abnormalities were combined in a proarrhythmic score, proportional to the incidence and amplitude of the abnormalities. This score significantly increases starting at concentrations ∼100-fold below that at which TdP/VF developed (P

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

Background To study segmental structural and functional aortic properties in Turner syndrome (TS) patients. Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome. Cardiovascular magnetic resonance (CMR) allows segmental study of aortic elastic properties. Method We performed Pulse Wave Velocity (PWV) and distensibility measurements using CMR of the thoracic and abdominal aorta in 55 TS-patients, aged 13-59y, and in a control population (n = 38;12-58y). We investigated the contribution of TS on aortic stiffness in our entire cohort, in bicuspid (BAV) versus tricuspid (TAV) aortic valve-morphology subgroups, and in the younger and older subgroups. Results Differences in aortic properties were only seen at the most proximal aortic level. BAV Turner patients had significantly higher PWV, compared to TAV Turner (p = 0.014), who in turn had significantly higher PWV compared to controls (p = 0.010). BAV Turner patients had significantly larger ascending aortic (AA) luminal area and lower AA distensibility compared to both controls (all p

Background Thoracic aortic aneurysm ( TAA ) outcomes are worse in women than men, although reasons for sex differences are unknown. Because faster TAA growth is a risk factor for acute aortic syndromes, we sought to determine the role of sex and aneurysm etiology on TAA growth. Methods and Results Eighty‐two consecutive unoperated subjects with TAA who had serial aneurysm measurements were recruited. In multivariable linear regression the association of female sex with aneurysm growth rate was assessed after adjustment for potential confounders. We also tested the interaction term sex×aneurysm etiology in the prediction of TAA growth. Seventy‐four percent of subjects were men; mean± SD age was 62.4±11.9 years in men and 67.7±10.7 years in women ( P =0.06). Forty‐seven (57%) subjects had degenerative TAA s, and the remainder had heritable TAA s. Absolute baseline aneurysm size and follow‐up time were not different between men and women. Aneurysm growth rate was 1.19±1.15 mm/y in women and 0.59±0.66 mm/y in men ( P =0.02). Female sex remained significantly associated with greater aneurysm growth in multivariable analyses (β± SE : 0.35±0.12, P =0.005). In addition, female sex was associated with faster TAA growth only among those with degenerative TAA (β± SE : 0.33±0.08, P =0.0002) and not among those with heritable TAA ( P =0.79), with a significant sex×etiology interaction ( P =0.001). Conclusions TAA growth rates are greater in women than men, and this difference is specific to women with degenerative TAA s. Our findings may explain sex differences in TAA outcomes and provide a foundation for future investigations of this topic.

Objective(s): Atherosclerotic disease is caused by a combination of systemic and local factors (e.g. geometry) affecting local flow conditions. In contrast to the carotid artery, at the iliac-femoral artery region, a large degree of bilateral asymmetry exists. Therefore, we aimed to determine the influence of body side on the prevalence of atherosclerosis (i.e. plaque and intima-media thickness; IMT) at the carotid and femoral arteries. Methods: Data were used from the ASKLEPIOS study, including 2524 apparently healthy individuals with a mean age of 46 years (range 35-55 years). Echographic images were obtained bilaterally of the carotid and femoral arteries. A single observer approach was used for the acquisition and quantification of plaques and IMT. Results: The carotid artery displays no significant left-right difference in IMT values nor plaque prevalence (right: 12.0 vs. left 13.3%; P - 0.18). In contrast, for the femoral artery, the IMT distribution at the right common femoral artery is more skewed (P90 right: 1.11mm, left 1.01mm; P< 0.001), which is mirrored by a significantly higher plaque prevalence (right: 21.9 vs. left: 15.7%; P< 0.001). Conclusion: In the present study, atherosclerotic lesions are more prevalent at the right than at the left femoral artery. This finding highlights the possible role of local arterial geometry in the development of atherosclerosis and underscores the importance of the choice of body side when assessing vascular health.

Introduction Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population. Methods In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400mg moxifloxacin administered on two occasions. Results In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5mgl-1 or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25mgl-1, standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78kg or higher, the probability of hitting this target approaches zero. Conclusions Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.

Purpose To assess the difference between thoracic and abdominal aortic pulse wave velocity (PWV) in apparently healthy subjects including young adults to elderly subjects. Materials and Methods We performed PWV and distensibility measurements and analysis of thoracic and abdominal aortic segments in 96 apparently normal subjects aged 20–80 years with magnetic resonance (MR). Both unadjusted correlation and General Linear Model (GLM) analysis of log-transformed PWV (thoracic and abdominal aorta) and distensibility (four aortic cross-sections) were performed. Results Both thoracic and abdominal PWV values and distensibility values increased with age. In unadjusted analyses the correlation between the ln(thoracic PWV) and age (r = 0.71; P

Objective: To test the hypothesis that Human Immunodeficiency Virus (HIV) infection in Black patients is associated with increased cardiometabolic risk factors that may increase aortic stiffness assessed by pulse wave velocity (PWV). Methods: We matched 96 Cameroonian Controls to 238 (Un) treated HIV-positive patients [HIV] for age. In each participant, aortic PWV (ComplioR), blood pressures (BP), lipid profile and fasting blood glucose (FPG) were measured. Results: Waist circumference was lower in HIV than in Controls (both p g·dl-1), and of diabetes (FPG > 125 mg·dl-1) were higher in HIV than in the Controls (50% vs 27%, and 23% vs 1%, respectively; both p p = 0.02). Fasting triglycerides (TG) and the atherogenic dyslipidemia ratio [log(TG)/HDL-C] were higher in HIV than in the Controls (both p p > 0.05). HIV patients exhibited a twice-higher prevalence of MetS (AHA/NHLBI score 33/5) than that of the Controls (41% vs 21%; p 0.01). Similarly, severity of MetS phenotype was higher in HIV as compared to the Controls (2.14% vs 1.59%; p p = 0.036). Conclusions: HIV infection is associated with higher prevalence of MetS and its phenotype in Black African patients that may induce increased aortic stiffness.

Hypertension (HTN) has the highest population-attributable risk for acute aortic syndromes and is highly prevalent among patients with thoracic aortic aneurysm (TAA). Although HTN is diagnosed based on brachial blood pressure (BP), this does not accurately correspond to central BP, which is of

Background Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism. Methods and results Experiments were executed in isolated female rabbit hearts perfused for 150 minutes with domperidone 30, 60, or 100 nM. Domperidone significantly prolonged the action potential duration: +9% at 30 nM, +32% at 60 nM, and +48% at 100 nM. Domperidone induced significant disturbances of repolarization in 83% of hearts at 60 nM and in 100% at 100 nM, including early afterdepolarizations and polymorphic ventricular tachycardia. Maximum therapeutic free drug plasma concentration of domperidone (19 nM) yields a safety index of only ∼2.5, that is, 12-fold below the accepted minimum. Gastrointestinal benefits and risks for SCD were derived from the literature. The defined daily dose of domperidone (30 mg/day) fails to show unequivocal gastrointestinal benefits beyond a placebo effect. In contrast, 5 of 5 population-based studies show that oral domperidone significantly increases the odds ratio for SCD to 2.8 (1.53-6.21) and it increases sharply above 30 mg/day. Conclusions Because domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine.

Pharmacopuncture treatments are proposed for cardiovascular disease and heart failure [1]. Heart failure results from complex environment-gene interactions. β-adrenergic receptors and protein kinase A (PKA) interact with histones and related segments of deoxyribonucleic acid (DNA) at promoter regions of genes for messenger ribo nucleic acid (mRNA) transcription. This increases cardiac muscle mass and contractility in normal hearts. In heart failure, activation of β-adrenergic receptors and PKA promote pathological hypertrophy and decreased contractility. Experimental models show that prenatal exposure to hypoxia, cocaine, or nicotine increases susceptibility to heart failure when animals reach adulthood. Hypermethylation of DNA is an epigenetic mechanism associated with downregulation of the protein kinase C (PKC) gene in such models of heart failure. Downregulation of PKC is also produced by the stress-related hormone norepinephrine with upregulation of the hypoxia-inducible differentiation regulator Nix in norepinephrine-induced cardiac fibrosis [2]. Norepinephrine is also the main mediator of sympathetic neural activity. Sympathetic neural overactivity, a significant cofactor in human heart failure, is, therefore, implicated as a cofactor in this epigenetic mechanism for heart failure. Other epigenetic mechanism for cardiac hypertrophy and heart failure involve endothelin- 1 induced downregulation of the cardiac myocyte differentiation factor RE1-silencing transcription signaler (REST) and GATA zinc-finger domain-containing protein-1 (GATAD1) induced inhibition of histone deacetylase (HDAC-2) in cardiac myocytes harvested from autosomal-recessive dilated cardiac myopathy patients with heart failure [3]. In contrast, both the HDAC-2 in cardiac myocytes and the HDAC-1 in cardiac fibroblasts are upregulated in experimental animal models of congestive heart failure [4]. A prominent role for inflammation in heart failure is suggested by tumor necrosis factor (TNF-α), a proinflammatory cytokine, inducing hypermethylation of the sarcoplasmic reticulum calcium ATPase (SERCA-2A) gene in cardiac myocytes, associated with diastolic dysfunction and heart failure. An important role for epigenetic mechanisms in heart failure is also suggested by HDAC-dependent stimulation of the stress-apoptosis intracellular signaling pathway, which induces hypertrophy of both cardiac and vascular smooth muscle [5].

Background : Since antidepressants are prescribed for multiple indications, the use of an antidepressant cannot be equated with a diagnosis of depression. Objective : The objective of this study was to examine the quality of antidepressant prescribing in Belgian nursing homes, with a critical evaluation of indications and dosages, to see whether depression was appropriately treated in terms of drug choice, the indications for which antidepressants were being prescribed and whether there was underdosing. Methods : This analysis was based on data obtained in the Prescribing in Homes for the Elderly in Belgium (PHEBE) study, a cross-sectional, descriptive study of a representative, stratified, random sample of 1,730 residents from 76 Belgian nursing homes. The PHEBE study investigated overall drug utilization in Belgian nursing homes in 2006. Clinical and medication data for the present study were obtained from this study. A 28-item checklist of clinical conditions was designed ad hoc for the PHEBE study and sent to the residents' general practitioners (GPs) to collect clinical information. We copied the residents' medication charts, classified the drugs using the Anatomical Therapeutic Chemical (ATC) classification system codes and transferred the drug names and dosages into a database. Information on indications was retrospectively obtained from the GPs, so that we could link the indication to each medication. Minimum effective doses (MEDs) of antidepressants to treat major depression were obtained from the literature to assess underdosing. Results : The overall use of antidepressants in nursing homes was 39.5 % (95 % CI 37.2, 41.8). The physicians classified 34.2 % (95 % CI 32.0, 36.4) of the residents as having depression, and 80.9 To of these patients were treated with an antidepressant. Indications among the single antidepressant users (n = 551) were depression (66.2 %), insomnia (13.4 %), anxiety (6.2 %) and neuropathic pain (1.6 %). In the indication of depression, 74.8 % used a selective serotonin reuptake inhibitor (SSRI), predominantly citalopram, sertraline and escitalopram. Venlafaxine was used by 10.7 % of the residents. Dosages for these antidepressants were equal to or higher than the MED. But when trazodone, amitriptyline or mirtazapine were used to treat depression, respectively, 92.3, 55.5 and 44.5 % of prescribed dosages were below the MED. In the indication of insomnia, most of the time, trazodone (90.5 %) or mirtazapine (5.4 %) were used, and in lower dosages than those required for depression treatment (

Aims Supravalvar aortic stenosis is a rare form of left ventricular outflow tract obstruction that is often progressive in childhood. Little data are available on outcomes in the adult population. Our aim was to define cardiac outcomes in adults with supravalvar aortic stenosis. Methods and results This is a multicentre retrospective study of cardiac outcomes in adults (≥18 years) with supravalvar aortic stenosis. We examined: (i) adverse cardiac events (cardiovascular death, myocardial infarction, stroke, heart failure, sustained arrhythmias, and infective endocarditis) and (ii) the need for cardiac surgery in adulthood. One hundred and thirteen adults (median age at first visit 19 years; 55% with Williams–Beuren syndrome; 67% with surgical repair in childhood) were identified. Adults without Williams–Beuren syndrome had more severe supravalvar aortic stenosis and more often associated left ventricular outflow tract obstructions ( P < 0.001). In contrast, mitral valve regurgitation was more common in patients with Williams–Beuren syndrome. Eighty-five per cent of adults (96/113) had serial follow-up information (median follow-up 6.0 years). Of these patients, 13% (12/96) had an adverse cardiac event and 13% (12/96) had cardiac operations (7 valve repair or replacements, 4 supravalvar aortic stenosis repairs, 1 other). Cardiac surgery was more common in adults without Williams–Beuren syndrome ( P = 0.007). Progression of supravalvar aortic stenosis during adulthood was rare. Conclusion Adults with supravalvar aortic stenosis remain at risk for cardiac complications and reoperations, while progression of supravalvar aortic stenosis in adulthood is rare. Valve surgery is the most common indication for cardiac surgery in adulthood.

Background— Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. Methods and Results— We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3′- BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, β=−0.075±0.012 SD/allele, P =2.8×10 −10 ; replication β=−0.086±0.020 SD/allele, P =1.4×10 −6 ). Combined results for rs7152623 from 11 cohorts gave β=−0.076±0.010 SD/allele, P =3.1×10 −15 . The association persisted when adjusted for mean arterial pressure (β=−0.060±0.009 SD/allele, P =1.0×10 −11 ). Results were consistent in younger (P =2.3×10 −9 ) and older (9 cohorts, n=12 026, β=−0.061±0.014 SD/allele, P =9.4×10 −6 ) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02–1.08; P =0.0013) and heart failure (hazard ratio=1.10, CI=1.03–1.16, P =0.004). Conclusions— Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.

Background: The current standard for arterial stiffness assessment, aortic pulse wave velocity (aPWV), is measured at diastolic pressure. Arterial stiffness, however, is pressure dependent. At the carotid artery level, the degree of this dependency can be quantified as the difference (Delta PWV) between systolic and diastolic (cPWV(d)) carotid pulse wave velocity. Biomechanically, a greater Delta PWV implies greater increases in left ventricular afterload with physical activity. Therefore, we hypothesized, that Delta PWV is more strongly associated with left ventricular mass index (LVMI) than aPWV and cPWV(d). Methods: In 1776 healthy individuals from the Asklepios cohort (age 35-55 years), Delta PWV was obtained from combined carotid artery ultrasound and tonometry recordings. Multiple linear regression analysis was performed to investigate the associations of Delta PWV, cPWV(d) and aPWV with LVMI, adjusting for age, sex, mean blood pressure (MBP), central pulse pressure, and other possible confounders. Results: DPWV was 2.4 +/- 1.2 m/s (mean +/- SD), ranging from 0.8 m/s, indicating almost constant arterial stiffness over the cardiac cycle, to 4.4 m/s, reflecting substantial pressure dependency. Delta PWV was significantly associated with LVMI (beta of 2.46 g/m(1.7) per m/s, P < 0.001), even after full adjustment (beta of 0.56 g/m(1.7) per m/s, P = 0.03). cPWV(d) and aPWV had clear crude associations with LVMI (P < 0.001), but lost significance after adjustment (beta of -0.48 and -0.33 g/m(1.7) per m/s, with P = 0.11 and 0.2, respectively). Conclusion: The change in arterial stiffness over the cardiac cycle, rather than diastolic stiffness, is independently associated with LVMI in healthy middle-aged individuals. Therefore, the pressure dependency of arterial stiffness should be considered in cardiovascular risk assessment.

Objective: To evaluate the remodeling of large arteries according to age at menopause, duration of menopause, and use of hormone therapy (HT). Design: A cross-sectional study consisting of baseline measurements of a multicentric randomized trial were used to evaluate arterial parameters. Setting: The study was conducted in France, Belgium, and the Netherlands in academic hospitals and private clinics. Patient(s): Postmenopausal women (n = 538) with mild hypercholesterolemia. Intervention(s): None. Main Outcome Measure(s): Common carotid artery intima-media thickness (CCA-IMT), central pulse pressure, and aortic stiffness (carotid-femoral pulse wave velocity) were measured and centrally controlled for quality. Multivariate regression analysis was used to assess the possible covariates associated with arterial parameters. Result(s): Women were 58 +/- 6 (mean +/- SD) years of age with an age of 50 +/- 5 at menopause and a mean duration of menopause of 8 +/- 7 years. Lower age at menopause, time since menopause, and absence of HT use were independently associated with worsening of the arterial parameters. After multivariate analysis, HT was associated with a lower CCA-IMT (-40 mu m [range -64 to -1]), whereas lower age at menopause and menopause duration were respectively associated with a CCA-IMT increase (25 mu m/5 y and 27 mm/5 y). Similarly, values of central pulse pressure and pulse wave velocity were lower in HT users (-3.1 mm Hg [-5.1 to -0.9] and -0.31 m/s [-0.63 to -0.02], respectively) but worsened with age at menopause and menopause duration. Conclusion(s): The age at menopause, the time since menopause, and the use of HT are independently associated with the thickening and stiffening of the large arteries. Clinical Trial Registration Number: NCT00163163. (Fertil Steril (R) 2011; 96: 1445-50.

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659–0.776) for pulse wave velocity, 0.670 (95% CI 0.604–0.736) for central augmentation pressure, and 0.595 (95% CI 0.529–0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104–1.649; P =0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219–1.814; P

Oxidative stress is a key factor driving the aging of cells and arteries. Studies suggest that white blood cell (WBC) telomere length is an index of systemic aging. We, therefore, investigated the association between WBC telomere length and oxidized-LDL, and vascular aging, expressed by the distensibility of the carotid artery. We studied a random population sample of 216 non-smokers and 89, smokers. In all subjects, age and gender- adjusted telomere length was inversely correlated with plasma oxidized-LDL (regression coefficient = -0.656 kb/mg/dL; p=0.0006). Independent of gender, age and mean blood pressure, carotid distensibility increased with telomere length (2.33+/- 1.18 10-3/kPa/kb; p=0.05) but decreased with higher plasma levels of oxidized LDL (-10.7+/- 3.91 10-3/kPa/ mg/dL; p=0.006). Adjusted for gender and age, smokers' telomere length was shorter (6.72 vs 6.91 kb; p=0.014) and plasma oxidized-LDL level higher (0.52 vs 0.46 mg/dL; p=0.03) than in non-smokers. Higher level of oxidized-LDL, is associated with shorter WBC telomeres and increased stiffness of the carotid artery. Smoking is marked by increased oxidative stress in concert with shortened WBC telomere length. ispartof: Frontiers in Bioscience vol:2 issue:3 pages:1164-1168 ispartof: location:Singapore status: published

Comprehensive imaging plays a central role in the detection, workup and management of pulmonary hypertension (PH). Determination of systolic pulmonary artery pressure by Doppler echocardiography continues to be the primary tool for the early detection of PH. Although systolic pulmonary artery pressure derived via measurement of tricuspid regurgitation velocity has an excellent correlation with invasive measurements, certain pitfalls must be recognized by the clinician. Recent work on novel indexes of right ventricular function and on the noninvasive assessment of pulmonary vascular resistance by echocardiography is promising. Computed tomography (CT) is increasingly being used in PH and is particularly useful in ruling out pulmonary parenchymal etiologies, and to detect potentially surgically treatable forms such as extracardiac left to right shunts and chronic thromboembolic PH. Cardiac magnetic resonance (CMR) imaging has also become an increasingly useful tool in clinical practice and is now considered by many to be the gold standard for the structural and functional evaluation of the right heart. Volumetric and functional assessment can be performed accurately and reproducibly with CMR imaging without radiation or the need for geometric assumptions. Recently, various morphometric variables on CT and CMR imaging have been shown to correlate well with invasive measurement of pulmonary artery pressure. With ongoing innovations in echocardiography, CT and CMR imaging, it is expected that these mutually complementary imaging techniques will play an increasingly important role in the patient with PH.

With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part II of the guidelines includes recommendations for the care of patients with left ventricular outflow tract obstruction and bicuspid aortic valve disease, coarctation of the aorta, right ventricular outflow tract obstruction, tetralogy of Fallot, Ebstein anomaly and Marfan's syndrome. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

Objectives Noninvasive estimation of central blood pressure (BP) from radial artery pressure waveforms is increasingly applied. We investigated the impact of radial artery waveform calibration on central BP assessment and calculated pressure amplification, with focus on the one-third rule used to estimate mean arterial BP (MAP). Methods Pressure waveforms were noninvasively measured at the radial and carotid arteries in 1873 individuals (age 45.8+/-6.1 years). Radial and carotid artery waveforms were calibrated using brachial artery DBP and SBP, MAP estimated with the one-third rule and MAP estimated as brachial DBP along with 40% of brachial artery pulse pressure. Results Central SBP obtained via a transfer function was 123.5 +/- 15.7, 117.8 +/- 14.2 and 126.0 +/- 15.4 mmHg (mean +/- SD) following above-mentioned three calibration schemes, respectively. Using the same calibration schemes, carotid artery SBP was 131.4 +/- 15.2, 118.4 +/- 14.4 and 126.8 +/- 15.7 mmHg, respectively. Central-to-brachial amplification was 13.0 +/- 3.6 mmHg using second method as compared with 4.6 +/- 3.8 mmHg with third method. Brachial-to-radial amplification was actually negative (-6.3 +/- 4.5 mmHg) using second method, whereas 3.4 +/- 5.5 mmHg was found with third method. Conclusion Both carotid artery SBP and central SBP obtained via a transfer function are highly sensitive to the calibration of the respective carotid artery and radial artery pressure waveforms. Our data suggest that the one-third rule to calculate MAP from brachial cuff BP should be avoided, especially when used to calibrate radial artery pressure waveforms for subsequent application of a pressure transfer function. Until more precise estimation methods become available, it is advisable to use 40% of brachial pulse pressure instead of 33% to assess MAP.

Background Carotid–femoral pulse wave velocity can be determined using different distances – either direct carotid–femoral distance or subtracted [(sternal–femoral) − (carotid–sternal)] distance – resulting in pulse wave velocity differences of up to 30%. The present study aims to present and validate a population-based model for the conversion between distances. Method Three thousand one hundred and sixteen participants from the Asklepios study (n = 2510) and Hopital Europeen Georges Pompidou (n = 606) databases, in which all distance measurements were available, were randomly distributed in a model (n = 311) and validation (n = 2805) population. Model parameters for the conversion equations were selected and evaluated using multiple linear regression with stepwise selection of covariates (age, sex, weight, height, BMI and waist circumference). The proposed model was evaluated on the validation population. Results The difference between direct and subtracted distances was found to be partially dependent on body height, and its inclusion in the multivariate model improved model performance by over 20%. Other combinations of adjustments did not improve model prediction. Conversion equations derived in the model population were: Estimated Direct_distance = 0.45*Subtracted_distance + 0.21*height + 0.08 and Estimated Subtracted_distance = 1.04*Direct_distance − 0.11*height − 0.02, respectively. Applying these equations for estimation of direct and subtracted distances in the validation population yielded good correspondence to measured results (r2 = 0.73 and 0.57, respectively), with nonsignificant mean differences between estimated and measured values. Increasing the size of the model population did not significantly change the model validity. Conclusion In cases in which not all distance measurements are available for exact conversion, the presented equations can be used to convert between distance definitions.

The relationship between aortic (carotid-femoral) pulse wave velocity and stiffness measures based on local diameter and pressure readings is not yet fully understood.We compared the relationship with age and gender of aortic pulse wave velocity to stiffness indices (compliance and distensibility coefficient) evaluated at the common carotid and femoral arteries in 2195 (1131 women) apparently healthy subjects, aged 35-55 years participating in the Asklepios study. Aortic pulse wave velocity was further compared with previously reported central arterial stiffness parameters on the same population. Subjects were divided into four age groups for analysis.Femoral arterial stiffness was higher in men than in women (P0.001) but did not change with age and no age-gender interaction was evident. Carotid arterial stiffness increased with age (P0.001) and showed a significant (P0.001) age-gender interaction, with carotid stiffness increasing more rapidly in women than in men, crossing over around the age of 45. Aortic pulse wave velocity did not differ between men and women, but did increase with age (P0.001). No age-gender interaction was evident.The relation with age and gender of local and central stiffness measures is not the same over the age range 35-55 in apparently healthy men and women. Depending on the central stiffness parameter used, age-gender effects evident at the carotid artery are or are not found centrally. Though the relevance of these differences requires further evaluation in a longitudinal study with outcome data, they need to be kept in mind when designing or interpreting results from arterial stiffness evaluation studies.