Gender differences of atrial and ventricular remodeling and autonomic tone in nonelite athletes

Veteran endurance athletes have an increased risk of developing atrial fibrillation (AF), with a striking male predominance. We hypothesized that male athletes were more prone to atrial and ventricular remodeling and investigated the signal-averaged P wave and factors that promote the occurrence of AF. Nonelite athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Of the 873 marathon and nonmarathon runners who were willing to participate, 68 female and 70 male athletes were randomly selected. The runners with cardiovascular disease or elevated blood pressure (>140/90 mm Hg) were excluded. Thus, 121 athletes were entered into the final analysis. Their mean age was 42 ± 7 years. No gender differences were found for age, lifetime training hours, or race time. The male athletes had a significantly longer signal-averaged P-wave duration (136 ± 12 vs 122 ± 10 ms; p <0.001). The left atrial volume was larger in the male athletes (56 ± 13 vs 49 ± 10 ml; p = 0.001), while left atrial volume index showed no differences (29 ± 7 vs 30 ± 6 ml/m²; p = 0.332). In male athletes, the left ventricular mass index (107 ± 17 vs 86 ± 16 g/m²; p <0.001) and relative wall thickness (0.44 ± 0.06 vs 0.41 ± 0.07; p = 0.004) were greater. No differences were found in the left ventricular ejection fraction (63 ± 4% vs 66 ± 6%; p = 0.112) and mitral annular tissue Doppler e' velocity (10.9 ± 1.5 vs 10.6 ± 1.5 cm/s; p = 0.187). However, the tissue Doppler a' velocity was higher (8.7 ± 1.2 vs 7.6 ± 1.3 cm/s; p < 0.001) in the male athletes. Male athletes had a higher systolic blood pressure at rest (123 ± 9 vs 110 ± 11 mm Hg; p < 0.001) and at peak exercise (180 ± 15 vs 169 ± 19 mm Hg; p = 0.001). In the frequency domain analysis of heart rate variability, the sympatho-vagal balance, represented by the low/high-frequency power ratio, was significantly greater in male athletes (5.8 ± 2.8 vs 3.9 ± 1.9; p < 0.001). Four athletes (3.3%) had at least one documented episode of paroxysmal AF, all were men (p = 0.042). In conclusion, for a comparable amount of training and performance, male athletes showed a more pronounced atrial remodeling, a concentric type of ventricular remodeling, and an altered diastolic function. A higher blood pressure at rest and during exercise and a higher sympathetic tone might be causal. The altered left atrial substrate might facilitate the occurrence of AF.

Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Outcome in adult patients after arterial switch operation for transposition of the great arteries

BACKGROUND: The arterial switch operation (ASO) is currently the treatment of choice in neonates with transposition of the great arteries (TGA). The outcome in childhood is encouraging but only limited data for long-term outcome into adulthood exist. METHODS AND RESULTS: We studied 145 adult patients (age>16, median 25years) with ASO followed at our institution. Three patients died in adulthood (mortality 2.4/1000-patient-years). Most patients were asymptomatic and had normal left ventricular function. Coronary lesions requiring interventions were rare (3 patients) and in most patients related to previous surgery. There were no acute coronary syndromes. Aortic root dilatation was frequent (56% patients) but rarely significant (>45mm in 3 patients, maximal-diameter 49mm) and appeared not to be progressive. There were no acute aortic events and no patient required elective aortic root surgery. Progressive neo-aortic-valve dysfunction was not observed in our cohort and only 1 patient required neo-aortic-valve replacement. Many patients (42.1%), however, had significant residual lesions or required reintervention in adulthood. Right ventricular outflow tract lesions or dysfunction of the neo-pulmonary-valve were frequent and 8 patients (6%) required neo-pulmonary-valve replacement. Cardiac interventions during childhood (OR 3.0, 95% CI 1.7-5.4, P<0.0001) were strong predictors of outcome (cardiac intervention/significant residual lesion/death) in adulthood. CONCLUSIONS: Adult patients with previous ASO remain free of acute coronary or aortic complications and have low mortality. However, a large proportion of patients require re-interventions or present with significant right sided lesions. Life-long cardiac follow-up is, therefore, warranted. Periodic noninvasive surveillance for coronary complications appears to be safe in adult ASO patients.

Control of ventricular unloading using an electrocardiogram-synchronized Thoratec paracorporeal ventricular assist device

OBJECTIVE: Current pulsatile ventricular assist devices operate asynchronous with the left ventricle in fixed-rate or fill-to-empty modes because electrocardiogram-triggered modes have been abandoned. We hypothesize that varying the ejection delay in the synchronized mode yields more precise control of hemodynamics and left ventricular loading. This allows for a refined management that may be clinically beneficial. METHODS: Eight sheep received a Thoratec paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, Calif) via ventriculo-aortic cannulation. Left ventricular pressure and volume, aortic pressure, pulmonary flow, pump chamber pressure, and pump inflow and outflow were recorded. The pump was driven by a clinical pneumatic drive unit (Medos Medizintechnik AG, Stolberg, Germany) synchronously with the native R-wave. The start of pump ejection was delayed between 0% and 100% of the cardiac period in 10% increments. For each of these delays, hemodynamic variables were compared with baseline data using paired t tests. RESULTS: The location of the minimum of stroke work was observed at a delay of 10% (soon after aortic valve opening), resulting in a median of 43% reduction in stroke work compared with baseline. Maximum stroke work occurred at a median delay of 70% with a median stroke work increase of 11% above baseline. Left ventricular volume unloading expressed by end-diastolic volume was most pronounced for copulsation (delay 0%). CONCLUSIONS: The timing of pump ejection in synchronized mode yields control over left ventricular energetics and can be a method to achieve gradual reloading of a recoverable left ventricle. The traditionally suggested counterpulsation is not optimal in ventriculo-aortic cannulation when maximum unloading is desired.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

BACKGROUND: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. METHODS: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. RESULTS: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. CONCLUSIONS: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Traumatic free wall and ventricular septal rupture - 'hybrid' management in a child

A 8-year-old boy showed a traumatic ventricular septal rupture following a blunt chest trauma, and was scheduled for elective catheter closure. Two weeks later, a follow-up echocardiogram revealed a pseudoaneurysm of the anterior wall of the left ventricle. Because of the apical location of the VSD, it was decided to proceed with transcatheter occlusion. After successful VSD closure, the patient was taken to the operation room for surgical repair of the left ventricular pseudoaneurysm. Symptoms and signs seen in patients with ventricular pseudoaneurysms appear to be discrete and variable, and a high clinical index of suspicion with a very close echocardiographic follow-up is strongly recommended after occurrence of a blunt cardiac trauma. The combined 'hybrid' approach of transcatheter closure of the intraventricular rupture followed by surgical closure of the pseudoaneurysm allows for a less invasive and efficient management of this rare combination of post-traumatic ventricular free wall and septal rupture in a child.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition. Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction<30%, pseudonormal or restrictive mitral inflow pattern at Doppler-echocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance<300 m or a peak oxygen uptake<12-14 ml/kg/min; 5) history of >1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

PURPOSE: The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. PATIENTS AND METHODS: The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. RESULTS: Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. CONCLUSION: Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

His-Purkinje system re-entry in patients with clustering ventricular tachycardia episodes

AIMS: Multiple arrhythmia re-inductions were recently shown in His-Purkinje system (HPS) ventricular tachycardia (VT). We hypothesized that HPS VT was a frequent mechanism of repetitive or incessant VT and assessed diagnostic criteria to select patients likely to have HPS VT. METHODS AND RESULTS: Consecutive patients with clustering VT episodes (>3 sustained monomorphic VT within 2 weeks) were included in the analysis. HPS VT was considered plausible in patients with (i) impaired left ventricular function associated with dilated cardiomyopathy or valvular heart disease; or (ii) ECG during VT similar to sinus rhythm QRS or to bundle-branch block QRS. HPS VT was plausible in 12 of 48 patients and HPS VT was demonstrated in 6 of 12 patients (50%, or 13% of the whole study group). Median VT cycle length was 318 ms (250-550). Catheter ablation was successful in all six patients. CONCLUSION: His-Purkinje system VT is found in a significant number of patients with repetitive or incessant VT episodes, and in a large proportion of patients with predefined clinical or electrocardiographic characteristics. Since it is easily amenable to catheter ablation, our data support the screening of all patients with repetitive VT in this regard and an invasive approach in a selected group of patients.

The Ross procedure in infants and young children

BACKGROUND: This study reviews our experience with the Ross procedure in infants and young children. METHODS: From September 1993 to September 2004, 52 children less than 15 years of age underwent a Ross procedure. The patients ranged in age from 4 days to 15 years old (median, 5 years). Fifteen patients (29%) were less than 2 years of age. The predominant indication for the Ross procedure was aortic stenosis. Sixteen patients underwent a Ross-Konno procedure for severe left ventricular outflow tract obstruction. Thirty-four patients had 48 previous interventions. Preoperatively, 6 patients showed severe left ventricular dysfunction, and 2 of the patients required ventilation and inotropic support. Concomitant procedures were performed in 8 patients. Three patients had a mitral valve replacement, 2 patients had a ventricular septal defect closure and an aortic arch reconstruction, 2 patients had aortic arch reconstructions, and 1 patient had resection of a coarctation and a ventricular septal defect closure. RESULTS: Patients were followed up for a median of 43 months (range, 1 to 130). Overall survival was 85% +/- 5% at 1 and 82% +/- 5% at 2, 5, and 10 years. Hospital mortality was 5 of 52 patients (9.6%). All deaths occurred in neonates or infants less than 2 months of age, who needed urgent surgery. Three patients died late of noncardiac causes. At last follow-up, all patients were classified in New York Heart Association functional class I or II. No patient had endocarditis of the autograft or the right ventricular outflow tract replacement. During the follow-up, no event of thrombembolism was observed. No patient required the insertion of a permanent pacemaker. Overall freedom from reoperation is 57% +/- 15% at 10 years. One patient required the replacement of the autograft at 6 months postoperatively. The development of mild aortic insufficiency was observed in 24 patients, and moderate aortic insufficiency in 1 patient during follow-up. Freedom from reoperation for the right ventricular outflow tract replacement is 60% +/- 15% at 10 years. CONCLUSIONS: The Ross procedure represents an attractive approach to aortic valve disease in young children. However, a high early mortality rate has to be considered when performing this procedure in neonates or infants who present in critical preoperative condition.

Noninvasive measurement of cardiac output during exercise by inert gas rebreathing technique

Reduced exercise tolerance and dyspnea during exercise are hallmarks of heart failure syndrome. Exercise capacity and various parameters of cardiopulmonary response to exercise are of important prognostic value. All the available parameters only indirectly reflect left ventricular dysfunction and hemodynamic adaptation to an increased demand. Noninvasive assessment of cardiac output, especially during an incremental exercise stress test, would allow the direct measure of cardiac reserve and may become the gold standard for prognostic evaluation in the future.

Reversal of myocyte hypertrophy by ventricular unloading: cardiac improvement without adrenergic receptor up-regulation and relocalization.

In previous studies, we found that the improved contractile ability of cardiac myocytes from patients who have had left ventricular assist device (LVAD) support was due to a number of beneficial changes, most notably in calcium handling (increased sarcoplasmic reticulum calcium binding and uptake), improved integrity of cell membranes due to phospholipid reconstruction (reduced lysophospholipid content), and an upregulation of adrenoreceptors (increased adrenoreceptor numbers). However, in the case presented here, there was no increase in adrenoreceptor number, which is something that we usually find in core tissue at the time of LVAD removal or organ transplantation; also, there was no homogeneous postassist device receptor distribution. However, the patient was well maintained for 10 months following LVAD implantation, until a donor organ was available, regardless of the lack of adrenoreceptor improvement. We conclude from these studies that cardiac recovery is the result of the initiation of multiple repair mechanisms, and that the lack of expected changes, in this case increased adrenoreceptors, is not always an accurate indicator of anticipated outcome. We suggest that interventions and strategies have to consider multiple, beneficial changes due to unloading and target a number of biochemical and structural areas to produce improvement, even if not all of these improvements occur.

Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

BACKGROUND The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. METHODS This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20-29, 30-49, 50-69, and ≥70 years) and cardiac measurements were compared using Pearson's rank correlation over the four different groups. RESULTS With advanced age a slight but significant decrease in ESV (r=-0.41 for both ventricles, P<0.001) and EDV (r=-0.39 for left ventricle, r=-0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). CONCLUSIONS The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies.

Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

BACKGROUND In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01166997.

Hemodynamic assessment of critically ill patients using a miniaturized transesophageal echocardiography probe.

INTRODUCTION Hemodynamic management in intensive care patients guided by blood pressure and flow measurements often do not sufficiently reveal common hemodynamic problems. Trans-esophageal echocardiography (TEE) allows for direct measurement of cardiac volumes and function. A new miniaturized probe for TEE (mTEE) potentially provides a rapid and simplified approach to monitor cardiac function. The aim of the study was to assess the feasibility of hemodynamic monitoring using mTEE in critically ill patients after a brief operator training period. METHODS In the context of the introduction of mTEE in a large ICU, 14 ICU staff specialists with no previous TEE experience received six hours of training as mTEE operators. The feasibility of mTEE and the quality of the obtained hemodynamic information were assessed. Three standard views were acquired in hemodynamically unstable patients: 1) for assessment of left ventricular function (LV) fractional area change (FAC) was obtained from a trans-gastric mid-esophageal short axis view, 2) right ventricular (RV) size was obtained from mid-esophageal four chamber view, and 3) superior vena cava collapsibility for detection of hypovolemia was assessed from mid-esophageal ascending aortic short axis view. Off-line blinded assessment by an expert cardiologist was considered as a reference. Inter-rater agreement was assessed using Chi-square tests or correlation analysis as appropriate. RESULTS In 55 patients, 148 mTEE examinations were performed. Acquisition of loops in sufficient quality was possible in 110 examinations for trans-gastric mid-esophageal short axis, 118 examinations for mid-esophageal four chamber and 125 examinations for mid-esophageal ascending aortic short axis view. Inter-rater agreement (Kappa) between ICU mTEE operators and the reference was 0.62 for estimates of LV function, 0.65 for RV dilatation, 0.76 for hypovolemia and 0.77 for occurrence of pericardial effusion (all P < 0.0001). There was a significant correlation between the FAC measured by ICU operators and the reference (r = 0.794, P (one-tailed) < 0.0001). CONCLUSIONS Echocardiographic examinations using mTEE after brief bed-side training were feasible and of sufficient quality in a majority of examined ICU patients with good inter-rater reliability between mTEE operators and an expert cardiologist. Further studies are required to assess the impact of hemodynamic monitoring by mTEE on relevant patient outcomes.