Percutaneous management of paravalvular leaks.

Paravalvular leak (PVL) is a challenging complication of valve replacement surgery that can cause heart failure and haemolysis. Surgical repair is the traditional treatment for severe, symptomatic PVL, but many patients with PVL fall into high-risk categories for redo surgery. Percutaneous techniques for closure of PVL have been increasingly refined over the last decade with availability of approved purpose-specific devices for closure. Percutaneous closure requires a heart team approach, with attention paid to appropriate preprocedural and periprocedural imaging to ensure a successful closure with minimal residual leak or complication. There are limited studies addressing the selection of a percutaneous approach to PVL. No randomised trials comparing surgical and percutaneous repair have been conducted. Large national registries from the UK and Ireland and from Spain have demonstrated that high rates of technical success can be achieved, with mortality comparable with surgical repair. Six retrospective studies comparing surgical and percutaneous approaches have been published. These broadly show comparable technical success between the interventions, with reduced short-term mortality among patients treated percutaneously. Long-term outcomes were similar between both treatment options. Percutaneous repair is an attractive treatment option in many patients due to its reduced invasiveness and quicker recovery period. However, more prospective studies are needed to validate its place in the armamentarium of the heart team.

Brief smoking cessation in acute Welsh hospitals: a realist approach.

This implementation study sought to determine what works to support brief smoking cessation (BSC) in acute hospital settings, through exploration of organizational delivery and the role of healthcare professionals (HCPs). We used a realist approach, with embedded stakeholder engagement, within a large health organization. We conducted interviews (n = 27), a survey (n = 279) and organization documentation review (n = 44). The final programme theory suggests HCPs implement BSC when they value it as part of their role in contributing to improved patient outcomes; this is due to personal and professional influences, such as knowledge or experience. Organizational support, training and working in an environment where BSC is visible as standard care, positively influences implementation. However, the context exerts a strong influence on whether BSC is implemented, or not. HCPs make nuanced judgements on whether to implement BSC based on their assessment of the patient's responses, the patient's condition and other acute care demands. HCPs are less likely to implement BSC in dynamic and uncertain environments, as they are concerned about adversely impacting on the clinician-patient relationship and prioritize other acute care requirements. Organizations should actively promote BSC as a core function of the acute hospital setting and improve professional practice through leadership, training, feedback and visible indicators of organizational commitment. HCPs can be persuaded that implementing BSC is an acute care priority and an expectation of standard practice for improving patient outcomes.

Markers of responsiveness to disopyramide in patients with hypertrophic cardiomyopathy.

BACKGROUND: Significant left-ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients, nearly 30% of HCM patients do not respond. We sought to study the clinical and echocardiographic variables associated with disopyramide-induced LVOT-gradient reduction. METHODS: Forty-one disopyramide-treated HCM patients (average daily-dose 305 mg) were subdivided into two groups: (1) nineteen responders, with a reduction of LVOT-gradients of at least 30% from baseline, and (2) twenty-two non-responders, in whom LVOT-gradients did not change or increased following treatment. All patients had a thorough clinical and echocardiographic assessment pre- and post-treatment initiation. RESULTS: Patients who responded to disopyramide had better pretreatment left ventricular (LV) systolic function (LV ejection fraction of 67.9 ±â€¯5.6% vs. 59.7 ±â€¯5.8%, p = 0.0001), better LV global longitudinal strain (-17.9 ±â€¯2.3% vs. -16.1 ±â€¯2.5%, p = 0.048), less mitral regurgitation, smaller LV size (indexed LV end-systolic volume of 16.2 ±â€¯5.1 ml/m2 vs. 23.2 ±â€¯6.8 ml/m2, p = 0.001), and lower LV maximal wall thickness (17.2±3 mm vs.19.2 ±â€¯3.4 mm, p = 0.046). Baseline left atrial (LA) volumes were significantly lower in the responders, with higher indices of LA ejection fraction (62 ±â€¯11.2% vs. 50.5 ±â€¯12.2%, p = 0.005), systolic LA strain (34 ±â€¯12.4% vs. 25.8 ±â€¯10.6%, p = 0.04), and LA strain-rate (1.34 ±â€¯0.49%/sec vs. 0.99 ±â€¯0.24%/sec, p = 0.012). In multivariable analysis, the presence of reduced LV systolic function and systolic LA strain-rate remained independently associated with poor response to disopyramide. CONCLUSIONS: Obstructive HCM patients with more severe disease at baseline tend to respond less to disopyramide treatment. In those patients, early referral for alcohol septal ablation or myectomy surgery should be considered.

Left atrial remodeling postseptal myectomy for severe obstructive hypertrophic cardiomyopathy: Analysis by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Septal myectomy relieves left ventricular outflow obstruction (LVOTO) and is associated with excellent long-term outcomes. LVOTO is associated with diastolic dysfunction and increased left atrial (LA) size. We sought to investigate the changes in LA volumes and function postmyectomy and the association between these changes with clinical outcomes postmyectomy. METHODS: Sixty-six hypertrophic cardiomyopathy patients undergoing myectomy were retrospectively studied. Preprocedural and 6- to 18-month postmyectomy follow-up transthoracic echocardiographic images were obtained. LA volumes and strain were assessed by two-dimensional speckle-tracking echocardiography. RESULTS: Left atrial volumes, that is, indexed maximal, minimal, and pre-A volumes reduced postmyectomy, yet remained increased compared to controls (105.6 ± 34.5 mL vs 84.9 ± 26.7 mL, 45.2 ± 25.7 mL vs 35.4 ± 22.6 mL, 70.1 ± 31.4 mL vs 35.4 ± 22.6 mL, respectively, P < 0.05). The total emptying index did not improve postmyectomy and remained lower than controls (58.6 ± 12.4 vs 59.9 ± 12.8, P = NS) whereas atrial contraction improved, yet did not normalize (active emptying index 36.1 ± 14.9 vs 41.1 ± 16.2, P < 0.05). The conduit volume remained reduced postmyectomy (18.6 ± 13.3 mL vs 16.6 ± 15.1 mL, P = NS). LA strain also did not improve postmyectomy (26.8 ± 7.3 vs 28.5 ± 8.8, P = NS). A multivariable logistic regression identified preprocedural E/e' ratio and indexed maximal LA volume, as independent predictors for LA volume reduction ≥20% postmyectomy. During a mean follow-up of 4.9 ± 2.3 years postmyectomy, 24.2% of the patients developed atrial fibrillation and <5% of patients were severely symptomatic. We found no associations between LA volumes/function and atrial fibrillation or symptoms postmyectomy. CONCLUSION: Postmyectomy LA volumes decreased, and the contractile function improved. There was no association between LA volumes/function and clinical outcomes postmyectomy. Notably, the LA remained enlarged (though to a lesser degree) with reduced strain and emptying fraction, suggesting possible atrial myopathy.

Arts-based palliative care training, education and staff development: A scoping review.

BACKGROUND: The experience of art offers an emerging field in healthcare staff development, much of which is appropriate to the practice of palliative care. The workings of aesthetic learning interventions such as interactive theatre in relation to palliative and end-of-life care staff development programmes are widely uncharted. AIM: To investigate the use of aesthetic learning interventions used in palliative and end-of-life care staff development programmes. DESIGN: Scoping review. DATA SOURCES: Published literature from 1997 to 2015, MEDLINE, CINAHL and Applied Social Sciences Index and Abstracts, key journals and citation tracking. RESULTS: The review included 138 studies containing 60 types of art. Studies explored palliative care scenarios from a safe distance. Learning from art as experience involved the amalgamation of action, emotion and meaning. Art forms were used to transport healthcare professionals into an aesthetic learning experience that could be reflected in the lived experience of healthcare practice. The proposed learning included the development of practical and technical skills; empathy and compassion; awareness of self; awareness of others and the wider narrative of illness; and personal development. CONCLUSION: Aesthetic learning interventions might be helpful in the delivery of palliative care staff development programmes by offering another dimension to the learning experience. As researchers continue to find solutions to understanding the efficacy of such interventions, we argue that evaluating the contextual factors, including the interplay between the experience of the programme and its impact on the healthcare professional, will help identify how the programmes work and thus how they can contribute to improvements in palliative care.

Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics.

BACKGROUND: Regional variability of longitudinal strain (LS) has been previously described with echocardiography in patients with cardiac amyloidosis (CA), however, the reason for this variability is not completely evident. We sought to describe regional patterns in LS using feature-tracking software applied to cardiovascular magnetic resonance (CMR) cine images in patients with CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry's disease (AFD) and to relate these patterns to the distribution of late gadolinium enhancement (LGE). METHODS: Patients with CA (n = 45) were compared to LV mass indexed matched patients with HCM (n = 19) and AFD (n = 19). Peak systolic LS measurements were obtained using Velocity Vector Imaging (VVI) software on CMR cine images. A relative regional LS ratio (RRSR) was calculated as the ratio of the average of the apical segmental LS divided by the sum of the average basal and mid-ventricular segmental LS. LGE was quantified for the basal, mid, and apical segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to RRSR. RESULTS: Patients with CA had significantly had worse global LS (-15.7 ± 4.6%) than those with HCM (-18.0 ± 4.6%, p = 0.046) and AFD (-21.9 ± 5.1%, p < 0.001). The RRSR was higher in patients with CA (1.00 ± 0.31) than in AFD (0.79 ± 0.24; p = 0.018) but not HCM (0.84 ± 0.32; p = 0.114). In CA, a regional difference in LGE burden was noted, with lower LGE in the apex (31.5 ± 19.1%) compared to the mid (38.2 ± 19.0%) and basal (53.7 ± 22.7%; p < 0.001 for both) segments. The regional LGE ratio was not significantly different between patients with CA (0.33 ± 0.15) and AFD (0.47 ± 0.58; p = 0.14) but lower compared to those with HCM (0.72 ± 0.43; p < 0.0001). LGE percentage showed a significant impact on LS (p < 0.0001), with a 0.9% decrease in absolute LS for every 10% increase in LGE percentage. CONCLUSION: The presence of marked "relative apical sparing" of LS along with a significant reduction in global LS seen in patients with CA on CMR cine analysis may provide an additional tool to differentiate CA from other cause of LVH. The concomitant presence of a base to apex gradient in quantitative LGE burden suggests that the regional strain gradient may be at least partially explained by the burden of amyloid deposition and fibrosis.

Diagnosis and assessment of dilated cardiomyopathy: a guideline protocol from the British Society of Echocardiography.

Heart failure (HF) is a debilitating and life-threatening condition, with 5-year survival rate lower than breast or prostate cancer. It is the leading cause of hospital admission in over 65s, and these admissions are projected to rise by more than 50% over the next 25 years. Transthoracic echocardiography (TTE) is the first-line step in diagnosis in acute and chronic HF and provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, valve function and the presence of pericardial effusion, while contributing to information on aetiology. Dilated cardiomyopathy (DCM) is the third most common cause of HF and is the most common cardiomyopathy. It is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment. This document provides a practical approach to diagnosis and assessment of dilated cardiomyopathy that is aimed at the practising sonographer.

An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer.

A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.

Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to determine whether short-term treatment with perhexiline improves cardiac energetics, left ventricular function, and symptoms of heart failure by altering cardiac substrate utilization. BACKGROUND: Perhexiline improves exercise capacity and left ventricular ejection fraction (LVEF) in patients with heart failure (HF). (31)P cardiac magnetic resonance spectroscopy can be used to quantify the myocardial phosphocreatine/adenosine triphosphate ratio. Because improvement of HF syndrome can improve cardiac energetics secondarily, we investigated the effects of short-term perhexiline therapy. METHODS: Patients with systolic HF of nonischemic etiology (n = 50, 62 ± 1.8 years of age, New York Heart Association functional class II to IV, LVEF: 27.0 ± 1.44%) were randomized to receive perhexiline 200 mg or placebo for 1 month in a double-blind fashion. Clinical assessment, echocardiography, and (31)P cardiac magnetic resonance spectroscopy were performed at baseline and after 1 month. A substudy of 22 patients also underwent cross-heart blood sampling at completion of the study to quantify metabolite utilization. RESULTS: Perhexiline therapy was associated with a 30% increase in the phosphocreatine/adenosine triphosphate ratio (from 1.16 ± 0.39 to 1.51 ± 0.51; p < 0.001) versus a 3% decrease with placebo (from 1.36 ± 0.31 to 1.34 ± 0.31; p = 0.37). Perhexiline therapy also led to an improvement in New York Heart Association functional class compared with placebo (p = 0.036). Short-term perhexiline therapy did not change LVEF. Cross-heart measures of cardiac substrate uptake and respiratory exchange ratio (which reflects the ratio of substrates used) did not differ between patients who received perhexiline versus placebo. CONCLUSIONS: Perhexiline improves cardiac energetics and symptom status with no evidence of altered cardiac substrate utilization. No change in LVEF is seen at this early stage. (Metabolic Manipulation in Chronic Heart Failure; NCT00841139).

Myocardial fibrosis in hypertrophic cardiomyopathy: accurate reflection of histopathological findings by CMR.

OBJECTIVES: In this study we sought to explore the relationship between cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and histopathological parameters including interstitial fibrosis and replacement fibrosis (scar) in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: CMR-LGE is a well-established tool for the assessment of scar in ischemic heart disease. Its role in HCM has evolved in recent years, and an association with nonsustained ventricular tachycardia has been demonstrated. METHODS: HCM patients who underwent septal myectomy during the period 2004 through 2010 and had undergone CMR-LGE no more than 6 months before surgery were selected. Histopathological assessment of the myectomy specimens included quantitative digital analysis (interstitial and replacement fibrosis) and semiquantitative assessment (small intramural coronary arteriole dysplasia and disarray). Correlations between CMR-LGE measured with various techniques, SD above the signal intensity for the normal remote myocardium (2, 4, 5, 6, and 10 SD) and the full width at half maximum (FWHM) technique, at the myectomy site, and interstitial fibrosis, replacement fibrosis (scar), and their sum (fibrosis + scar) were evaluated. RESULTS: Twenty-nine patients were included. Statistically significant correlations between CMR-LGE (at 2, 4, 5, 6, 10 SD and by the FWHM technique), and both interstitial fibrosis and the combined interstitial and replacement fibrosis were found. The strongest correlation was between combined interstitial and replacement fibrosis and CMR-LGE measured at 5 SD (r = 0.78, p < 0.0001). LGE measured at 10 SD demonstrated the best correlation with replacement fibrosis (r = 0.42, p = 0.02). Bland-Altman analysis revealed optimum agreement between the combined interstitial and replacement fibrosis found at pathology and LGE measured at 4 SD. In addition, moderate and severe small intramural coronary artery dysplasia showed a statistically significant correlation with replacement fibrosis (p = 0.01) and CMR-LGE at 10 SD (p = 0.04). CONCLUSIONS: CMR-LGE measured at 4 SD and 5 SD yields the closest approximation to the extent of total fibrosis measured by the histopathological standard of reference. These findings have implications for future investigations of CMR-LGE and its association with important clinical endpoints in HCM, including sudden cardiac death.

The fate of abstracts presented at annual meetings of the Society for Cardiothoracic Surgery in Great Britain and Ireland from 1993 to 2007.

Although the presentation of original research to learned societies is valuable, the target should be publication in a peer-reviewed journal. Therefore, the strength of a meeting may be assessed by the rate of the subsequent publication of papers from the presented abstracts. We conducted an analysis of abstracts presented at consecutive annual meetings of the Society for Cardiothoracic Surgery (SCTS) in Great Britain and Ireland over a 15-year period. Abstract books and other documentation from the 1993-2007 meetings were reviewed; abstracts from other major Cardiothoracic Surgery meetings held in 2007 were also reviewed. Medline was searched to identify the peer-reviewed publications arising from each work presented. For abstracts presented at SCTS in 2003-07, the factors potentially associated with publication were analysed by logistic regression. If no publications were identified, authors were contacted through a standardized email questionnaire to ascertain its status and reasons for non-publication. Over the 15-year period, 909 abstracts were presented at the SCTS meetings. The rate of publication rose from ~30% in the mid-1990s to consistently >60% from recent meetings, with a high of 81.3% from 2006. However, in comparison with other Cardiothoracic Surgery meetings in 2007, the chance of subsequent publication from SCTS (66.7%) was lower than from the European Association for Cardio-Thoracic Surgery (75.0%), the American Association for Thoracic Surgery (83.9%) and The Society of Thoracic Surgeons (72.5%) meetings. For abstracts presented at the last five SCTS meetings, publication was most commonly in a speciality journal (56.3%) and the median time for publication was 15 months (range -24 to 63 months) with 14 papers published prior to presentation at the meeting. On regression analysis, the only factor associated with publication was the study design comparing randomized trials and systematic reviews with other types of study (P < 0.01). Of the 90 unpublished abstracts, 48 (53.3%) authors replied to an email questionnaire revealing that 41 (85.4%) were never submitted for publication. The most common reasons given were low priority (29.6%) and low likelihood of acceptance (24.1%). In recent years, the annual meeting of the Society has become a forum for the presentation of high-quality research that usually withstands peer-review, most commonly in a speciality journal. The rate of publication has increased to consistently >60%, although those that remain unpublished are generally never submitted. This compares favourably with national meetings of other surgical societies, although it is lower than other major cardiothoracic meetings which have an affiliated journal. At a time when it has been suggested that medical research in the UK is in decline, cardiothoracic surgery appears to be thriving.

Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial.

BACKGROUND: Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and ß-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. METHODS: A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN72887836.

Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial.

BACKGROUND: Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked ß-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.

Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency.

OBJECTIVES: We sought to evaluate the role of exercise-related changes in left ventricular (LV) relaxation and of LV contractile function and vasculoventricular coupling (VVC) in the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and to assess myocardial energetic status in these patients. BACKGROUND: To date, no studies have investigated exercise-related changes in LV relaxation and VVC as well as in vivo myocardial energetic status in patients with HFpEF. METHODS: We studied 37 patients with HFpEF and 20 control subjects. The VVC and time to peak LV filling (nTTPF, a measure of LV active relaxation) were assessed while patients were at rest and during exercise by the use of radionuclide ventriculography. Cardiac energetic status (creatine phosphate/adenosine triphosphate ratio) was assessed by the use of (31)P magnetic resonance spectroscopy at 3-T. RESULTS: When patients were at rest, nTTPF and VVC were similar in patients with HFpEF and control subjects. The cardiac creatine phosphate/adenosine triphosphate ratio was reduced in patients with HFpEF versus control subjects (1.57 +/- 0.52 vs. 2.14 +/- 0.63; p = 0.003), indicating reduced energy reserves. Peak maximal oxygen uptake and the increase in heart rate during maximal exercise were lower in patients with HFpEF versus control subjects (19 +/- 4 ml/kg/min vs. 36 +/- 8 ml/kg/min, p < 0.001, and 52 +/- 16 beats/min vs. 81 +/- 14 beats/min, p < 0.001). The relative changes in stroke volume and cardiac output during submaximal exercise were lower in patients with HFpEF versus control subjects (ratio exercise/rest: 0.99 +/- 0.34 vs. 1.25 +/- 0.47, p = 0.04, and 1.36 +/- 0.45 vs. 2.13 +/- 0.72, p < 0.001). The nTTPF decreased during exercise in control subjects but increased in patients with HFpEF (-0.03 +/- 12 s vs. +0.07 +/- 0.11 s; p = 0.005). The VVC decreased on exercise in control subjects but was unchanged in patients with HFpEF (-0.01 +/- 0.15 vs. -0.25 +/- 0.19; p < 0.001). CONCLUSIONS: Patients with HFpEF have reduced cardiac energetic reserve that may underlie marked dynamic slowing of LV active relaxation and abnormal VVC during exercise.

Profiles of inflammatory cytokines following colorectal surgery: relationship with wound healing and outcome.

Inflammation is an essential component of normal wound healing. This study has correlated systemic (plasma) and local (wound fluid) concentrations of inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha [TNF-alpha], and IL-1beta) with wound healing and surgical outcome following elective colorectal surgery. Paired plasma and wound fluid samples were collected (n = 44) postoperatively (days 1, 3, 5, 7) and analyzed by enzyme-linked immunosorbent assay (pg/mL). Cytokine levels were significantly greater in drain fluid than plasma on each postoperative day (POD); e.g., POD 1 : IL-6; drain fluid, median, 77,050 pg/mL (range 9,928-456,408); plasma, 241 pg/mL (22-1,333). Daily profiles of IL-6 and TNF-alpha were similar in drain fluid and plasma; IL-6 levels peaked on POD 1 decreasing to POD 7, and TNF-alpha levels increased from PODs 1 to 7. However, IL-1beta in plasma peaked on POD 1 and plateaued, whereas drain fluid showed two peaks (PODs 1 and 7). Only plasma levels of cytokines correlated to clinical parameters; IL-6 levels significantly correlated with postoperative complications; e.g., POD 5, complications 92(1-597) and no complications, 14(2-217). IL-6 also correlated with tumor pathology (Dukes stage, tumor depth, vascular invasion), and TNF-alpha levels correlated with the estimated blood loss during surgery. We conclude that local wound levels of cytokines correlated with the stage of wound healing, whereas systemic levels correlated with postoperative complications and tumor pathology.

Reversal of inappropriate peripheral vascular responses in hypertrophic cardiomyopathy.

OBJECTIVES: We assessed the frequency of abnormal forearm vasodilator responses during lower body negative pressure (LBNP) in 21 non-obstructive hypertrophic cardiomyopathy (HCM) patients (31 +/- 8 [20 to 43] years) with abnormal blood pressure response (ABPR) to exercise and the effects of three drugs used to treat vasovagal syncope (propranolol, clonidine, and paroxetine) in a double-blind crossover study. BACKGROUND: Some HCM patients have an ABPR to exercise, which may be due to paradoxical peripheral vasodilatation. A similar proportion has paradoxical forearm vasodilatation during central volume unloading using LBNP. These abnormal reflexes may be caused by left ventricular mechanoreceptor activation. Similar mechanisms may also contribute to some cases of vasovagal syncope. METHODS: Blood pressure changes were assessed during exercise, and forearm vascular responses and baroreceptor sensitivity were assessed during LBNP using plethysmography. RESULTS: Nine (43%) patients (group A) had paradoxical vasodilator responses (forearm vascular resistance [FVR] fell by 7.5 +/- 4.6 U), and 12 (57%) patients (group B) had normal vasoconstrictor responses during LBNP (FVR increased by 7.7 +/- 4.9 U). Paroxetine augmented systolic blood pressure (SBP) during exercise in group A (21 +/- 6 mm Hg vs. 14 +/- 11 mm Hg at baseline, p = 0.02); no effect was detected in group B. Paroxetine reversed paradoxical vascular responses during LBNP in seven (78%) patients from group A. Propranolol and clonidine had no significant effect on SBP during exercise but reversed paradoxical vascular responses in some patients from group A (n = 5 and n = 3). CONCLUSIONS: Paradoxical vasodilatation during LBNP occurs in 40% of patients with ABPR during exercise and is reversed by propranolol, clonidine, and paroxetine. Paroxetine also improved SBP response to exercise.