Notch ratio in pulmonary flow predicts long-term survival after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Assessment of the pattern of the RV outflow tract Doppler provides insights into the hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). We studied whether pre-operative assessment of timing of the pulmonary flow systolic notch by Doppler echocardiography is associated with long-term survival after pulmonary endarterectomy (PEA) for CTEPH. METHODS: Fifty-nine out of 61 consecutive CETPH patients (mean age 53 ± 14 years, 34% male) whom underwent PEA between June 2002 and June 2005 were studied. Clinical, echocardiographic and hemodynamic variables were assessed pre-operatively and repeat echocardiography was performed 3 months after PEA. Notch ratio (NR) was assessed with pulsed Doppler and calculated as the time from onset of pulmonary flow until notch divided by the time from notch until end of pulmonary flow. Long-term follow-up was obtained between May 2021 and February 2022. RESULTS: Pre-operative mean pulmonary artery pressure (mPAP) was 45 ± 15 mmHg and pulmonary vascular resistance (PVR) was 646 ± 454 dynes.s.cm-5. Echocardiography before PEA showed that 7 patients had no notch, 33 had a NR < 1.0 and 19 had a NR > 1.0. Three months after PEA, echocardiography revealed a significant decrease in sPAP in long-term survivors with a NR < 1.0 and a NR > 1.0, while a significant increase in TAPSE/sPAP was only observed in the NR < 1.0 group. Mean long-term clinical follow-up was 14 ± 6 years. NR was significantly different between survivors and non-survivors (0.73 ± 0.25 vs. 1.1 ± 0.44, p < 0.001) but no significant differences were observed in mPAP or PVR. Long-term survival at 14 years was significantly better in patients with a NR < 1.0 compared to patients with a NR > 1.0 (83% vs. 37%, p = < 0.001). CONCLUSION: Pre-operative assessment of NR is a predictor of long-term survival in CTEPH patients undergoing PEA, with low mortality risk in patients with NR < 1.0. Long-term survivors with a NR < 1.0 and NR > 1.0 had a significant decrease in sPAP after PEA. However, the TAPSE/sPAP only significantly increased in the NR < 1.0 group. In the NR < 1.0 group, the 6-min walk test increased significantly between pre-operative and at 1-year post-operative follow-up. NR is a simple echocardiographic parameter that can be used in clinical decision-making for PEA.

Worsening tricuspid regurgitation after ICD implantation is rather due to transvenous lead than natural progression.

BACKGROUND: Transvenous implantable cardioverter-defibrillators (TV-ICDs) are associated with greater tricuspid regurgitation (TR) severity, which leads to increased mortality. The pathophysiology is assumed to be lead-related, hence, treatment includes lead extraction. However, TR may also naturally occur in the high-risk ICD population, or may be caused by right ventricular pacing. We sought to evaluate the effect of ICD type (with or without lead) and pacing percentage on post-implantation TR severity. METHODS: In this retrospective cohort study, consecutive patients were included with a primary S-ICD or TV-ICD implantation between 2009 and 2019 and echocardiography studies ≤3 months before and ≤ 3 years post-implantation. The effect of ICD type on TR severity at follow-up was estimated adjusting for ventricular pacing percentage and potential confounders. The effect of ventricular pacing percentage on TR severity at follow-up was adjusted for potential confounders. RESULTS: 118 patients were included (mean age 52 ± 21): 31 (26%) with an S-ICD and 87 (74%) with a TV-ICD. Median 20 months post-implantation, worsening TR was found in 11/31 (34%) S-ICD patients and 45/87 (52%) TV-ICD patients (p = 0.15). Adjusted for age, atrial fibrillation, baseline TR and mitral regurgitation, ventricular pacing percentage, ICD dwelling time, BMI, hypertension and left ventricular ejection fraction, TV-ICDs were significantly associated with greater TR severity (OR 9.90, p = 0.002). Ventricular pacing percentage was very low, and not significantly associated with greater TR severity (OR 0.95, p = 0.066). CONCLUSIONS: Our results suggest that greater TR severity in ICD patients is mainly caused by the transvenous lead, rather than natural progression in the ICD population.

Can stress echocardiography identify patients who will benefit from percutaneous mitral valve repair?

The aim of the current study was to investigate whether stress echocardiography improves selection of patients who might have clinical benefit from percutaneous mitral valve repair with the MitraClip. In total, 39 patients selected for MitraClip implantation underwent preprocedural low-dose stress (dobutamine or handgrip) echocardiography from which stroke volume, ejection fraction and MR grade were measured. Outcome after MitraClip implantation was determined by New York Heart Association classification and Quality of Life questionnaires. Clinical benefit from MitraClip treatment was defined as survival and NYHA class I-II at 6 months follow-up. In total, 36 patients with a technically successful procedure were included in the analysis (mean age 79 ± 8 years, 47% male, 50% functional MR). Clinical benefit was achieved in 18 patients. All seven patients with MR decreasing during stress remained in NYHA III-IV or died within 6 months, while 62% (18 out of 29) of the patients with stable or increased MR during stress had clinical benefit (p = 0.008). Significant increase in Quality of Life on 4/8 subscales of the RAND Short Form-36 questionnaire was observed: Physical Functioning (p < 0.001), Social Functioning (p < 0.001), Mental Health (p = 0.022) and Vitality (p = 0.026) was seen in patients with an increase in stroke volume during stress echocardiography. Patients with a decreased MR during preprocedural stress echocardiography remained more symptomatic than patients with a stable or increased MR during stress. Stress echocardiography may support patient selection for percutaneous mitral valve repair.

Induced Hypertension for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Induced hypertension is widely used to treat delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage, but a literature review shows that its presumed effectiveness is based on uncontrolled case-series only. We here report clinical outcome of aneurysmal subarachnoid hemorrhage patients with DCI included in a randomized trial on the effectiveness of induced hypertension. METHODS: Aneurysmal subarachnoid hemorrhage patients with clinical symptoms of DCI were randomized to induced hypertension or no induced hypertension. Risk ratios for poor outcome (modified Rankin Scale score >3) at 3 months, with 95% confidence intervals, were calculated and adjusted for age, clinical condition at admission and at time of DCI, and amount of blood on initial computed tomographic scan with Poisson regression analysis. RESULTS: The trial aiming to include 240 patients was ended, based on lack of effect on cerebral perfusion and slow recruitment, when 21 patients had been randomized to induced hypertension, and 20 patients to no hypertension. With induced hypertension, the adjusted risk ratio for poor outcome was 1.0 (95% confidence interval, 0.6-1.8) and the risk ratio for serious adverse events 2.1 (95% confidence interval, 0.9-5.0). CONCLUSIONS: Before this trial, the effectiveness of induced hypertension for DCI in aneurysmal subarachnoid hemorrhage patients was unknown because current literature consists only of uncontrolled case series. The results from our premature halted trial do not add any evidence to support induced hypertension and show that this treatment can lead to serious adverse events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01613235.

Determinants of Gadolinium-Enhancement of the Aneurysm Wall in Unruptured Intracranial Aneurysms.

BACKGROUND: Recent studies suggest that gadolinium-enhancement of the aneurysm wall may reflect aneurysm wall inflammation, which might increase the risk of aneurysm growth or rupture. OBJECTIVE: To determine the prevalence of gadolinium-enhancement and its determinants in patients with predominantly small (<7 mm) unruptured intracranial aneurysms. METHODS: We performed 3 T MRI aneurysm wall imaging in patients with ≥1 unruptured aneurysm. With Poisson regression analysis, we calculated crude and adjusted risk ratios (RRs) with 95% confidence intervals (CI) to assess determinants of gadolinium-enhancement. RESULTS: Gadolinium-enhancement was observed in 25/79 patients (32%; 95% CI: 21%-42%) and 26/89 aneurysms (29%; 95% CI: 20%-39%). With aneurysms 1.0-2.9 mm as reference, RRs were 4.6 (95% CI: 0.6-36.5) for 3.0 to 4.9 mm, 9.4 (95% CI: 1.3-67.2) for 5.0 to 6.9 mm, and 14.8 (95% CI: 2.1-104.6) for ≥7.0 mm. With internal carotid artery as reference, RRs adjusted for aneurysm size were 3.6 (95% CI: 1.1-11.4) for posterior communicating artery and 3.0 (95% CI: 1.0-8.6) for middle cerebral artery. RRs were 0.8 (95% CI: 0.4-1.8) for acetylsalicylic acid use, 0.9 (95% CI: 0.5-1.8) for statin use, 1.4 (95% CI: 0.7-2.8) for hypertension, 0.9 (95% CI: 0.4-1.8) for previous smoking, 0.9 (95% CI: 0.3-2.6) for never smoking, and 1.4 (95% CI: 0.7-2.7) for irregular aneurysm shape. CONCLUSION: Approximately one-third of patients had gadolinium-enhancement. Because aneurysm size is the strongest determinant of gadolinium-enhancement and also an established predictor for aneurysm growth and rupture, prospective studies with serial imaging need to investigate if gadolinium-enhancement predicts aneurysm growth and rupture.

Risk Factors for Intracranial Aneurysm Rupture: A Systematic Review.

BACKGROUND: Intracranial aneurysm rupture prediction is poor, with only a few risk factors for rupture identified and used in clinical practice. OBJECTIVE: To provide an overview of all the risk factors (including genetic, molecular, morphological, and hemodynamic factors) that have potential for use in clinical practice. METHODS: We systematically searched PubMed and EMBASE and focused on factors that can be easily assessed in clinical practice, might be used for rupture prediction in clinical practice, and/or are potential targets for further research. Studies were categorized according to methodological quality, and a meta-analysis was performed, if possible. RESULTS: We included 102 studies describing 144 risk factors that fulfilled predefined criteria. There was strong evidence for the morphological factors irregular shape (studied in 4 prospective cohort studies of high-quality, pooled odds ratio [OR] of 4.8 [95% confidence interval 2.7-8.7]), aspect ratio (pooled OR 10.2 [4.3-24.6]), size ratio, bottleneck factor, and height-to-width ratio to increase rupture risk. Moderate level of evidence was found for presence of contact with the perianeurysmal environment (pooled OR 3.5 [1.4-8.4]), unbalanced nature of this contact (pooled OR 17.8 [8.3-38.5]), volume-to-ostium ratio, and direction of the aneurysm dome (pooled OR 1.5 [1.2-1.9]). CONCLUSION: Irregular aneurysm shape was identified as a risk factor with potential for use in clinical practice. The risk factors aspect ratio, size ratio, bottleneck factor, height-to-width ratio, contact with the perianeurysmal environment, volume-to-ostium ratio, and dome-direction should first be confirmed in multivariate analysis and incorporated in prediction models.

Comparative Ultrastructural and Stereological Analyses of Unruptured and Ruptured Saccular Intracranial Aneurysms.

Insight into processes leading to rupture of intracranial aneurysms (IAs) may identify biomarkers for rupture or lead to management strategies reducing the risk of rupture. We characterized and quantified (ultra)structural differences between unruptured and ruptured aneurysmal walls. Six unruptured and 6 ruptured IA fundi were resected after microsurgical clipping and analyzed by correlative light microscopy for quantitative analysis (proportion of the vessel wall area) and transmission electron microscopy for qualitative ultrastructural analysis. Quantitative analysis revealed extensive internal elastic lamina (IEL) thickening in ruptured IA (36.3% ± 15%), while thin and fragmented IEL were common in unruptured IA (5.6% ± 7.1%). Macrophages were increased in ruptured IA (28.3 ± 24%) versus unruptured IA (2.7% ± 5.5%), as were leukocytes (12.85% ± 10% vs 0%). Vasa vasorum in ruptured but not in unruptured IA contained vast numbers of inflammatory cells and extravasation of these cells into the vessel wall. In conclusion, detection of thickened IEL, leaky vasa vasorum, and heavy inflammation as seen in ruptured IA in comparison to unruptured IA may identify aneurysms at risk of rupture, and management strategies preventing development of vasa vasorum or inflammation may reduce the risk of aneurysmal rupture.

Vessel wall perforation mechanism of the excimer laser-assisted non-occlusive anastomosis technique.

The excimer laser assisted non-occlusive anastomosis (ELANA) technique is used to make anastomoses on intracerebral arteries. This end-to-side anastomosis is created without temporary occlusion of the recipient artery using a 308-nm excimer laser with a ring-shaped multi-fiber catheter to punch an opening in the arterial wall. Over 500 patients have received an ELANA bypass. However, the vessel wall perforation mechanism of the laser catheter is not known exactly and not 100 % successful. In this study, we aimed to understand the mechanism of ELANA vessel perforation using specialized imaging techniques to ultimately improve its effectiveness. High-speed imaging, high-contrast imaging, and high-sensitivity thermal imaging were used to study the laser wall perforation mechanism and reveal the mechanical and thermal effects involved. In vitro, rabbit arteries were exposed with the special designed laser catheter in a setup representative for the clinical setting, in which blood was replaced with a transparent UV absorbing liquid for visualization. We observed that laser vessel wall perforation was caused by explosive vapor bubbles tearing through the vessel wall, mostly within the first 20 of the total 200 pulses. Thermal effects were minimal. Unsymmetrical tension in the vessel wall inducing migration of the flap during laser exposure was observed in case of unsuccessful wall perforations. The laser wall perforation mechanism in the ELANA technique is primarily mechanical. Symmetric tension in the recipient vessel wall is essential and should be trained by neurosurgeons.

RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.

BACKGROUND AND PURPOSE: Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. METHODS: We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. RESULTS: We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. CONCLUSIONS: For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture.

Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: The presumed effectiveness of induced hypertension for treating delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is based on uncontrolled case-series only. We assessed the effect of induced hypertension on cerebral blood flow (CBF) in aneurysmal subarachnoid hemorrhage patients with delayed cerebral ischemia in a randomized clinical trial. METHODS: Aneurysmal subarachnoid hemorrhage patients were randomized to induced or no induced hypertension (control group) at delayed cerebral ischemia onset. CBF was assessed, blinded for treatment allocation, with computed tomographic perfusion in standardized predefined regions at delayed cerebral ischemia onset and after 24 to 36 hours of study treatment. Mean arterial blood pressure was compared between groups (linear mixed model). The primary outcome measure was the difference in change in overall CBF (Mann-Whitney U test). RESULTS: Mean arterial blood pressure was, on average, 12 mm Hg (95% confidence interval, 8.6-14.5) higher in the hypertension group (n=12) than in the control group (n=13). Change in overall CBF (mL/100g per s) was -8.5 (range, -42 to 30) in the control group and 0.1 (range, -31-43) in the hypertension group (P=0.25). CONCLUSIONS: Change in overall CBF did not differ to a statistically significant extent between the groups. Based on our results, 225 to 250 patients per group are needed to find a statistically significant difference in change in overall CBF between induced hypertension and no hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT0161323.

Seasonal Abundance of Mango Fruit Flies (Diptera: Tephritidae) and Ecological Implications for Their Management in Mango and Cashew Orchards in Benin (Centre & North).

We report the results of a large-scale (six orchards) and long-term (5-yr) study on seasonal population fluctuations of fruit flies (Diptera Tephritidae) in mango (2005-2009) and cashew (2007-2009) orchards in the Borgou Department, Benin.During the five consecutive years of mango fruit fly monitoring, 25 tephritid species were captured including three species of Bactrocera, 11 of Ceratitis, and 11 of Dacus, which is represented by 2,138,150 specimens in mango orchards. We observed significant differences in Bactrocera dorsalis (Hendel) counts between "high" and "low" mango production years from 2005 to 2008 but not in Ceratitis cosyra (Walker) counts. The native species, C. cosyra, the most abundant species during the dry season, peaked beginning of May, while the exotic species, B. dorsalis, the most abundant species during the rainy season, peaked in June. Preliminary results underlined the role of nine species of wild hosts and seven species of cultivated ones around mango orchards that played an important role in maintaining B. dorsalis in this Sudan zone all year round. The presence of C. cosyra stretched over 9 mo.During the first 14 wk of tephritid monitoring on cashew orchards situated near mango orchards, most flies (62%) were captured in traps positioned in cashew orchards, showing the strong interest of an early fly control on cashew before the mango season. According to these results, in the Sudan zone, effective and compatible control methods as proposed by the IPM package validated by the West African Fruit Fly Initiative project against mango fruit flies are proposed for a large regional tephritid control program in same zones of West Africa.

Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms.

BACKGROUND AND PURPOSE: The eventual goal of preventive treatment of unruptured intracranial aneurysms is to increase the number of life years with high life satisfaction. Insight in the time with reduced functioning, working capacity, and life satisfaction after aneurysm treatment is pivotal to balance the pros and cons of preventive aneurysm occlusion. METHODS: We sent a questionnaire on time-to-recovery to preintervention functioning and return-to-work and life satisfaction to patients treated for an unruptured aneurysm between 2000 and 2013. Changes in life satisfaction before treatment, during recovery, and at follow-up were assessed with Wilcoxon signed-rank tests. RESULTS: The questionnaire was sent to 159 patients of whom 110 (69%) responded. The mean follow-up time after aneurysm treatment was 6 years (SD 4). Fifty-four patients had endovascular and 56 had microsurgical occlusion. Complete recovery to preintervention functioning was reported by 81% (95% confidence interval [CI], 74-88) of patients, with a median time-to-recovery of 3 months (range 0-48). Complete work recovery was reported by 78% (95% CI, 66-87) of patients. The proportion of patients with high life satisfaction reduced from 76% (95% CI, 67-84) before treatment to 52% (95% CI, 43-61) during the period of recovery (P<0.01) and restored largely at long-term follow-up (67% [95% CI, 59-76], P=0.08). CONCLUSION: Life satisfaction is significantly reduced during the period of recovery after treatment of unruptured aneurysms. In the long-term, ≈1 out of 5 patients reports incomplete recovery. These treatment effects should be kept in mind when considering preventive aneurysm treatment. Prospective studies are needed to better compare these losses in patients treated for unruptured aneurysms with those who had subarachnoid hemorrhage.

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in clinically relevant changes in the dose distribution of radiotherapy. METHODS: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. RESULTS: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7-73.8 ml, p<0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11-26 mmHg, p<0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2-14 mmHg, p=0.008) and an increase in heart rate with 6 beats/min (95% CI 1-11 beats/min, p=0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. CONCLUSION: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated.

Visualization of the aneurysm wall: a 7.0-tesla magnetic resonance imaging study.

BACKGROUND: Risk prediction of rupture of intracranial aneurysms is poor and is based mainly on lumen characteristics. However, characteristics of the aneurysm wall may be more informative predictors. The limited resolution of currently available imaging techniques and the thin aneurysm wall make imaging of wall thickness challenging. OBJECTIVE: To introduce a novel protocol for imaging wall thickness variation using ultra--high-resolution 7.0-Tesla (7.0-T) magnetic resonance imaging (MRI). METHODS: We studied 33 unruptured intracranial aneurysms in 24 patients with a T1-weighted 3-dimensional magnetization-prepared inversion-recovery turbo-spin-echo whole-brain sequence with a resolution of 0.8 × 0.8 × 0.8 mm. We performed a validation study with a wedge phantom and with 2 aneurysm wall biopsies obtained during aneurysm treatment using ex vivo MRI and histological examination and correlating variations in MRI signal intensity with variations in actual thickness of the aneurysm wall. RESULTS: In vivo, the aneurysm wall was visible in 28 of the 33 aneurysms. Variation in signal intensity was observed in all visible aneurysm walls. Ex vivo MRI showed variation in signal intensity across the wall of the biopsies, similar to that observed on the in vivo images. Signal intensity and actual thickness in both biopsies had a linear correlation, with Pearson correlation coefficients of 0.85 and 0.86. CONCLUSION: Unruptured intracranial aneurysm wall and its variation in thickness can be visualized with 7.0-T MRI. Aneurysm wall thickness variation can now be further studied as a risk factor for rupture in prospective studies.

Electrophysiologic remodeling of the left ventricle in pressure overload-induced right ventricular failure.

OBJECTIVES: The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload. BACKGROUND: The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene expression, due to atrophic remodeling. LV atrophy is associated with electrophysiologic remodeling. METHODS: We conducted epicardial mapping in Langendorff-perfused hearts, patch-clamp studies, gene expression studies, and protein level studies of the LV in rats with pressure-induced RVF (monocrotaline [MCT] injection, n = 25; controls with saline injection, n = 18). We also performed epicardial mapping of the LV in patients with RVF after chronic thromboembolic pulmonary hypertension (CTEPH) (RVF, n = 10; no RVF, n = 16). RESULTS: The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90% repolarization and effective refractory periods (ERPs) (60 ± 1 ms vs. 44 ± 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 ± 2 cm/s vs. 70 ± 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 ± 0.01 vs. 0.11 ± 0.02; p < 0.05). Conduction slowing was not explained by impaired impulse formation, as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of Scn5a were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 ± 0.7 µm vs. 122.0 ± 0.4 µm; p = 0.02) and width (21.9 ± 0.2 µm vs. 25.3 ± 0.3 µm; p = 0.002), and impaired cell-to-cell impulse transmission (24% reduction in Connexin-43 levels). The LV of patients with CTEPH with RVF also exhibited ERP prolongation (306 ± 8 ms vs. 268 ± 5 ms; p = 0.001) and conduction slowing (53 ± 3 cm/s vs. 64 ± 3 cm/s; p = 0.005). CONCLUSIONS: Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.

Adults with Down syndrome have reduced cardiac response after light exercise testing.

OBJECTIVE: Physical fitness is reduced in adults with Down syndrome (DS). The present study was conducted to elucidate the exercise response in adults with DS. DESIGN: Case controlled before-after trial. SETTING: Residential centre for people with intellectual disabilities. PARTICIPANTS: 96 Adults with DS, 25 non-DS adults with an intellectual disability, 33 controls. INTERVENTIONS: Echocardiography to exclude heart defects and to measure cardiac index (CI) in the supine position, supine position with raised legs, and following ten knee bends. MAIN OUTCOME MEASURE: Exercise testing RESULTS: At rest, mean CI was not significantly different between persons with DS and controls (2.3 vs. 2.4 l/min/m(2), p = 0.3). However, mean CI after exercise was significantly lower in DS (2.9 vs. 3.7 l/min/m(2), p < 0.001) and mean CI increase from rest to exercise was more than 50% lower in DS. On the contrary, CI after exercise was similar among controls and non-DS adults with an intellectual disability. Significantly lower stroke volumes in DS were found with insufficient heart rate response. CONCLUSIONS: CI at rest was similar in adults with DS and controls; however persons with DS have a diminished cardiac response to exercise. Stroke volumes were significantly lower in DS during exercise and a compensated heightened heart rate was absent.

Patency, flow, and endothelialization of the sutureless Excimer Laser Assisted Non-occlusive Anastomosis (ELANA) technique in a pig model.

OBJECT: The purpose of this study was to assess flow, patency, and endothelialization of bypasses created with the sutureless Excimer Laser Assisted Non-occlusive Anastomosis (SELANA) technique in a pig model. METHODS: In 38 pigs, a bypass was made on the left common carotid artery (CCA), using the right CCA as a graft, with 2 SELANAs. Bypass flow was measured using single-vessel flowmetry. The pigs were randomly assigned to 1 of 12 survival groups (1, 2, 3, 4, 5, 6, 7, and 10 days; 2 and 3 weeks; and 3 and 6 months). One extra animal underwent the procedure and then was killed after 1 hour of bypass patency to serve as a control. Angiography was performed just before the animals were killed, to assess bypass patency. Scanning electron microscopy and histological studies were used to evaluate the anastomoses after planned death. RESULTS: The mean SELANA bypass flow was not significantly different from the mean flow in the earlier ELANA (Excimer Laser Assisted Non-occlusive Anastomosis) pig study at opening and follow-up. Overall SELANA bypass patency (87%) was not significantly different from the ELANA patency of 86% in the earlier study. Complete SELANA endothelialization was observed after 2-3 weeks, compared with 2 weeks in the earlier ELANA study. CONCLUSIONS: The SELANA technique is not inferior to the current ELANA technique regarding flow, patency, and endothelialization. A pilot study in patients is a logical next step.

Right ventricular pacing improves haemodynamics in right ventricular failure from pressure overload: an open observational proof-of-principle study in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Right ventricular (RV) failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH), and other types of pulmonary arterial hypertension is associated with right-to-left ventricle (LV) delay in peak myocardial shortening and, consequently, the onset of diastolic relaxation. We aimed to establish whether RV pacing may resynchronize the onsets of RV and LV diastolic relaxation, and improve haemodynamics. METHODS AND RESULTS: Fourteen CTEPH patients (mean age 63.7 ± 12.0 years, 10 women) with large (≥60 ms) RV-to-LV delay in the onset of diastolic relaxation (DIVD, diastolic interventricular delay) were studied. Temporary RV pacing was performed by atrioventricular (A-V) sequential pacing with incremental shortening of A-V delay to advance RV activation. Effects were assessed using tissue Doppler echocardiography and LV pressure-conductance catheter measurements in a subset of patients. Compared with right atrial pacing, RV pacing at optimal A-V delay (average 140 ± 22 ms, range 120-180 ms) resulted in significant DIVD reduction (59 ± 19 to 3 ± 22 ms, P < 0.001), and increase in LV stroke volume as measured by LV outflow tract velocity-time integral (14.9 ± 2.8 to 16.9 ± 3.0 cm, P < 0.001), along with enhanced global RV contractility and LV diastolic filling. CONCLUSION: Right-to-left ventricle resynchronization of the onset of diastolic relaxation results in stroke volume increase in CTEPH patients. Whether RV pacing may be a novel therapeutic target in RV failure following chronic pressure overload remains to be investigated.