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1.  Assessment of a University of California, Los Angeles 4‐Variable Risk Score for Advanced Heart Failure 
The 4‐variable risk score from University of California, Los Angeles (UCLA) demonstrated superior discrimination in advanced heart failure, compared to established risk scores. However, the model has not been externally validated, and its suitability as a selection tool for heart transplantation (HT) and left ventricular assist device (LVAD) is unknown.
Methods and Results
We calculated the UCLA risk score (based on B‐type natriuretic peptide, peak VO2, New York Heart Association class, and use of angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker) in 180 patients referred for HT. The outcome was survival free from urgent transplantation or LVAD. The model‐predicted survival was compared to Kaplan‐Meier's estimated survival at 1, 2, and 3 years. Model discrimination and calibration were assessed. During a mean follow‐up of 2.1 years, 37 (21%) events occurred. One‐, 2‐ and 3‐year observed event‐free survival was 88%, 81%, and 75%, and the observed/predicted ratio was 0.97, 0.96, and 0.97, respectively. Time‐dependent receiver operating characteristic curve analyses demonstrated good discrimination overall (1‐year area under curve, 0.801; 2‐year, 0.774; 3‐year, 0.837), but discrimination between the 2 highest risk groups was poor. The difference between observed and predicted survival ranged from −14 to +17 percentage points, suggesting poor model calibration. Fairly similar results were found when the analyses were repeated in 715 patients after multivariate imputation of missing data.
The UCLA 4‐variable risk model calibration was inconsistent and high‐risk discrimination was poor in an external validation cohort. Further model assessment is warranted before widespread use.
PMCID: PMC4309113  PMID: 24906370
heart failure; heart transplantation; prognostic risk models
2.  Sex differences in response to maximal exercise stress test in trained adolescents 
BMC Pediatrics  2012;12:127.
Sex comparisons between girls and boys in response to exercise in trained adolescents are missing and we investigated similarities and differences as a basis for clinical interpretation and guidance.
A total of 24 adolescent females and 27 adolescent males aged 13–19 years underwent a maximal bicycle exercise stress test with measurement of cardiovascular variables, cardiac output, lung volumes, metabolic factors/lactate concentrations and breath-by-breath monitoring of ventilation, and determination of peak VO2.
Maximum heart rate was similar in females (191 ± 9 bpm) and males (194 ± 7 bpm), cardiac index at maximum exercise was lower in females (7.0 ± 1.0 l/min/m2) than in males (8.3 ± 1.4 l/min/m2, P < 0.05). Metabolic responses and RQ at maximum exercise were similar (females: 1.04 ± 0.06 vs. males: 1.05 ± 0.05). Peak VO2 was lower in females (2.37 ± 0.34 l/min) than in males (3.38 ± 0.49 l/min, P < 0.05). When peak VO2 was normalized to leg muscle mass sex differences disappeared (females: 161 ± 21 ml/min/kg vs. males: 170 ± 23 ml/min/kg). The increase in cardiac index during exercise is the key factor responsible for the greater peak VO2 in adolescent boys compared to girls.
Differences in peak VO2 in adolescent boys and girls disappear when peak VO2 is normalized to estimated leg muscle mass and therefore provide a tool to conduct individual and intersex comparisons of fitness when evaluating adolescent athletes in aerobic sports.
PMCID: PMC3472286  PMID: 22906070
Adolescent; Sex; Body composition; Exercise stress test; ECG; Blood pressure; Peak VO2; Ventilation; Lactate
3.  Myocardial recovery in peri-partum cardiomyopathy after continuous flow left ventricular assist device 
Left ventricular assist devices (LVADs) offer effective therapy for severe heart failure (HF) as bridge to transplantation or destination therapy. Rarely, the sustained unloading provided by the LVAD has led to cardiac reverse remodelling and recovery, permitting explantation of the device. We describe the clinical course of a patient with severe peri-partum cardiomyopathy (PPCM) rescued with a continuous flow LVAD, who experienced recovery and explantation. We discuss assessment of and criteria for recovery.
PMCID: PMC3256109  PMID: 22082339
Peri-partum cardiomyopathy; heart failure; recovery; left ventricular assist device; mechanical circulatory support
5.  Ghrelin resistance occurs in severe heart failure and resolves after heart transplantation 
European Journal of Heart Failure  2009;11(8):789-794.
Severe heart failure (HF) is often associated with cachexia that reverses post-heart transplantation (HTx) with frequent development of obesity. Ghrelin is a novel appetite-stimulating hormone. The aim was to determine the role of ghrelin in regulating appetite, food intake, and body composition in HF and post-HTx.
Methods and results
We measured serial ghrelin, hunger sensation, caloric intake, and body composition in 12 HF patients awaiting HTx, 12 patients 12.7 ± 8.6 months post-HTx, and 7 controls. Seven of 12 HF patients were followed for longitudinal analysis post-HTx. Body mass index was 23.1 ± 3.1 in HF and 31.5 ± 5.5 post-HTx (P < 0.001). Heart transplantation patients had gained 18.0 ± 7.7 kg since HTx. Ghrelin area under the curve between controlled meals (control: 186 ± 39; HF: 264 ± 71; HTx: 194 ± 47 ng min/mL, P < 0.007) was higher in HF, but test meal caloric intake (control: 1185 ± 650; HF: 391 ± 103; HTx: 831 ± 309 kcal, P < 0.008) was lower in HF. The longitudinal analysis confirmed these findings.
Heart failure may be associated with resistance to the appetite-stimulating effects of ghrelin, which may contribute to cachexia. Heart transplantation may be associated with resolution of ghrelin resistance, which may contribute to weight gain. These findings are preliminary and should be confirmed in larger trials.
PMCID: PMC2715223  PMID: 19556330
Ghrelin; Heart failure; Cachexia; Heart transplantation; Weight gain; Appetite
6.  Growth hormone resistance in severe heart failure resolves after cardiac transplantation 
European Journal of Heart Failure  2009;11(5):525-528.
Severe heart failure (HF) is associated with cachexia; this is often reversed post cardiac transplantation (HTx) with frequent development of obesity. Growth hormone (GH) resistance is common in HF and may contribute to cachexia. Whether GH resistance resolves post HTx is unknown. We aimed to confirm that HF is associated with GH resistance and to test the hypothesis that GH resistance resolves post HTx.
Methods and results
We measured GH, insulin-like growth factor-1 (IGF-1), and body composition in 10 HF patients awaiting HTx, in 18 patients 11 ± 8 months post HTx, and seven controls. Body mass index was 23.5 ± 3.2 in HF patients and 29.3 ± 5.7 post HTx. HTx patients had gained 14 ± 8 kg since HTx. GH was elevated in HF (control: 0.21 ± 0.25; HF: 1.13 ± 1.19; HTx: 0.11 ± 0.13 ng/mL; P < 0.007), while IGF-1 was higher in HTx (control: 114 ± 57; HF: 94 ± 52; HTx: 190 ± 106 ng/mL; P < 0.02). HTx had higher total body and abdominal fat %.
GH resistance is present in severe HF and resolves post HTx. These findings should be confirmed through larger trials.
PMCID: PMC2671964  PMID: 19380328
Heart failure; Cachexia; Cardiac transplantation; Growth hormone; Insulin-like growth factor-1
7.  Rationale and design of the Karolinska-Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction 
European Journal of Heart Failure  2009;11(2):198-204.
Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF.
Methods and results
We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction ≥ 45%, brain natriuretic peptide (BNP) > 100 pg/mL or NT-proBNP > 300 pg/mL. Once stabilized, 4–8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers.
KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.
PMCID: PMC2639424  PMID: 19168519
Heart failure; Preserved ejection fraction; Diastolic dysfunction; Dyssynchrony; Echocardiography

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