Croat Med J. 2009 Apr; 50(2): 133-42Klemen P, Golub M, Grmec SAim. To determine the diagnostic accuracy of the combination of quantitative capnometry (QC), N-terminal pro-brain natriuretic peptide (NT-proBNP), and clinical assessment in differentiating heart failure (HF)-related acute dyspnea from pulmonary-related acute dyspnea in a pre-hospital setting. Methods. This prospective study was performed in the Center for Emergency Medicine Maribor, Slovenia, January 2005 - June 2007. Two groups of patients with acute dyspnea apnea were compared: HF-related acute dyspnea group (n = 238) vs pulmonary-related acute dyspnea (asthma/COPD) group (n = 203). The primary outcome was the comparison of combination of QC, NT-proBNP, and clinical assessment vs NT-proBNP alone or NT-proBNP in combination with clinical assessment, in differentiating HF-related acute dyspnea from pulmonary-related acute dyspnea (asthma/COPD) in pre-hospital emergency setting, using the area under the receiver operating characteristic curve (AUROC). The secondary outcomes end points were identification of independent predictors for final diagnosis of acute dyspnea (caused by acute HF or pulmonary diseases), and determination of NT-proBNP levels, as well as capnometry, in the subgroup of patients with a previous history of HF and in the subgroup of patients with a previous history of pulmonary disease. Results. In differentiating between cardiac and respiratory causes of acute dyspnea in pre-hospital emergency setting, NT-proBNP in combination with PetCO2 and clinical assessment (AUROC, 0.97; 95% confidence interval [CI], 0.90-0.99) was superior to combination of NT-proBNP and clinical assessment (AUROC, 0.94; 95% CI, 0.88-0.96; P = 0.006) or NT-proBNP alone (AUROC, 0.90; 95% CI, 0.85-0.94; P = 0.005). The values of NT-proBNP>/=2000 pg/mL and PetCO2

Clin Nurse Spec. 2009 May-Jun; 23(3): 138-44Rohyans LM, Pressler SJPURPOSE:: The purpose of this study was to determine the differences in depressive symptoms among a sample of heart failure outpatients by examining sociodemographic and clinical variables: sex, race, marital status, living arrangement/status, heart failure severity, and age. The most frequently reported depressive symptoms were also examined. DESIGN:: A descriptive, cross-sectional design was used. SETTING:: Patients were enrolled in a larger research study from 5 clinics in the Midwest (1 adult primary care medicine clinic, 1 heart clinic, and 3 heart failure clinics). SAMPLE:: The sample included 150 patients with mean age of 61.3 years; 88 (59%) were men, and 62 (41%) were women; 47 (31%) were African American, 101 (67%) were white, and 2 (2%) were Asian patients. Forty-seven percent of the patient sample were New York Heart Association class III. Approximately half (51%) of the patient sample were married. METHODS:: The Patient Health Questionnaire 8 was used to measure depressive symptoms. Heart failure severity was assessed using the New York Heart Association classification. FINDINGS:: Patients with class III and IV had significantly more depressive symptoms than patients with class I and II (P < .0001). Age was negatively correlated with depressive symptoms scores (P < .0002). There were no significant differences in depressive symptoms among the variables of sex, race, marital status, or living arrangement. The most frequently reported depressive symptom was "feeling tired/no energy." CONCLUSIONS:: The findings from this study may contribute to the development of a broader knowledge base regarding depressive symptoms and its correlates in heart failure and may be used as a foundation for further research.

Circulation. 2009 Apr 27; Michels G, Khan IF, Endres-Becker J, Rottlaender D, Herzig S, Ruhparwar A, Wahlers T, Hoppe UCBACKGROUND: -Impairment of intracellular Ca(2+) homeostasis and mitochondrial function has been implicated in the development of cardiomyopathy. Mitochondrial Ca(2+) uptake is thought to be mediated by the Ca(2+) uniporter (MCU) and a thus far speculative non-MCU pathway. However, the identity and properties of these pathways are a matter of intense debate, and possible functional alterations in diseased states have remained elusive. Methods and Results-By patch clamping the inner membrane of mitochondria from nonfailing and failing human hearts, we have identified 2 previously unknown Ca(2+)-selective channels, referred to as mCa1 and mCa2. Both channels are voltage dependent but differ significantly in gating parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single-channel amplitude, shorter openings, a lower open probability, and 3 to 5 subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and reduced only by very high concentrations (10 micromol/L). Both mitochondrial Ca(2+) channels are unaffected by blockers of other possibly Ca(2+)-conducting mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart conditions, making them less effective for Ca(2+) uptake and likely Ca(2+)-induced metabolism. Conclusions-Thus, we conclude that the human mitochondrial Ca(2+) uptake is mediated by these 2 distinct Ca(2+) channels, which are functionally impaired in heart failure. Current properties reveal that the mCa1 channel underlies the human MCU and that the mCa2 channel is responsible for the ruthenium red-insensitive/low-sensitivity non-MCU-type mitochondrial Ca(2+) uptake.

Iran J Kidney Dis. 2009 Apr; 3(2): 61-70Mahapatra HS, Lalmalsawma R, Singh NP, Kumar M, Tiwari SCVery often, physicians confront with patients who have concomitant heart and kidney failure. The coexistence of kidney and heart failure carries an extremely bad prognosis. The exact cause of deterioration of kidney function and the mechanism underlying this interaction are complex, multifactorial in nature, and still not completely understood. Both the heart and the kidney act in tandem to regulate blood pressure, vascular tone, diuresis, natriuresis, etc. An extension to the Guytonian model of volume and blood pressure control is proposed called cardiorenal connection. Regulating actions of Guyton's model were coupled to their extended actions on structure and function of the heart and the kidney changes in the rennin-angiotensin-aldosterone system, the imbalance between nitric oxide and reactive oxygen species, the sympathetic nervous system, and inflammation are the cardiorenal connectors to develop cardiorenal syndrome. Imbalance in this closed complex will often lead to deterioration of both cardiac and kidney function. The World Congress of Nephrology emphasized vast interrelated derangements that can occur in cardiorenal syndrome and proposed that the recent definition of cardiorenal syndrome be modified into categories whose labels reflect the likely primary and secondary pathology and time frame. For management, drugs that impair kidney function are undesirable, particularly in a population with already compromised or at risk of kidney function. In severe volume-loaded patients who are refractory to diuretics, management of cardiorenal dysfunction is challenging. In the absence of definitive clinical trials, treatment decision must be based on a combination of patient's condition and understanding of individual treatment options.

Am J Physiol Heart Circ Physiol. 2009 Apr 24; Shabbir A, Zisa D, Suzuki G, Lee THeart failure carries a poor prognosis with few treatment options. While myocardial stem cell therapeutic trials have traditionally relied on intracoronary infusion or intramyocardial injection routes, these cell delivery methods are invasive and can introduce harmful scar tissue, arrhythmia, calcification, or microinfarction in the heart. Given that patients with heart failure are at an increased surgical risk, development of a non-invasive stem cell therapeutic approach is logistically appealing. Taking advantage of the trophic effects of bone marrow mesenchymal stem cells (MSCs) and using a hamster heart failure model, the present study demonstrates a novel non-invasive therapeutic regimen via direct delivery of MSCs into the skeletal muscle bed. Intramuscularly injected MSCs and MSC-conditioned medium each significantly improved ventricular function one month after MSC administration. MSCs at 4 million cells per animal increased fractional shortening by ~40%, enhanced capillary and myocyte nuclear density by ~30% and ~80%, attenuated apoptosis by ~60%, and reduced fibrosis by ~50%. Myocyte regeneration is evidenced by a ~2-fold increase in expression of cell cycle markers and ~13% reduction in mean myocyte diameter. Increased circulating levels of hepatocyte growth factor (HGF), leukemia inhibitory factor (LIF), and macrophage colony-stimulating factor (M-CSF) were associated with mobilization of c-kit(+), CD31(+), and CD133(+) progenitor cells and subsequent increase in myocardial c-kit(+) cells. Trophic effects of MSCs further activated expression of HGF, insulin-like growth factor-2 (IGF-2), and vascular endothelial growth factor (VEGF) in the myocardium. The work highlights a cardiac repair mechanism mediated by trophic cross-talks between the injected MSCs, bone marrow, and heart that can be explored for non-invasive stem cell therapy. Key words: heart failure, non-invasive, mesenchymal stem cell.

Int J Qual Health Care. 2009 Apr 24; Filardo G, Nicewander D, Herrin J, Edwards J, Galimbertti P, Tietze M, McBride S, Gunderson J, Collinsworth A, Haydar Z, Williams J, Ballard DJOBJECTIVE: /st> To investigate the effectiveness of a quality improvement educational program in rural hospitals. DESIGN: /st> Hospital-randomized controlled trial. SETTING: PARTICIPANTS: /st> A total of 47 rural and small community hospitals in Texas that had previously received a web-based benchmarking and case-review tool. INTERVENTION: /st> The 47 hospitals were randomized either to receive formal quality improvement educational program or to a control group. The educational program consisted of two 2-day didactic sessions on continuous quality improvement techniques, followed by the design, implementation and reporting of a local quality improvement project, with monthly coaching conference calls and annual follow-up conclaves. MAIN OUTCOME MEASURES: /st> Performance on core measures for community-acquired pneumonia and congestive heart failure were compared between study groups to evaluate the impact of the educational program. RESULTS: /st> No significant differences were observed between the study groups on any measures. Of the 23 hospitals in the intervention group, only 16 completed the didactic program and 6 the full training program. Similar results were obtained when these groups were compared with the control group. CONCLUSIONS: /st> While the observed results suggest no incremental benefit of the quality improvement educational program following implementation of a web-based benchmarking and case-review tool in rural hospitals, given the small number of hospitals that completed the program, it is not conclusive that such programs are ineffective. Further research incorporating supporting infrastructure, such as physician champions, financial incentives and greater involvement of senior leadership, is needed to assess the value of quality improvement educational programs in rural hospitals.

Am J Physiol Heart Circ Physiol. 2009 Apr 24; Gademan MG, van Bommel RJ, Borleffs CJ, Man SC, Haest JC, Schalij MJ, van der Wall EE, Bax JJ, Swenne CABackground In a previous study we demonstrated that institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after institution of cardiac resynchronization therapy (CRT) has predictive value for mid-term response. Methods One day after implantation of a CRT device in 33 CHF patients (27 male / 6 female, age 66.5 +/- 9.5 years, left ventricular ejection fraction 28 +/- 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched-on and switched-off (on/off order randomized). Echocardiography was performed prior to implantation (baseline) and 6 months after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end systolic volume (LVESV) at follow-up had decreased by >/= 15%. Results Responders (69.7%) and non-responders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% (P=0.03); this differed significantly (P=0.02) from the average BRS change (-2%) in the non-responders. Also, CRT increased HRV by 30% in responders (P=0.02), but there was no significant difference found compared to the increase in HRV (8%) in the non-responders. Receiver-operating characteristic (ROC) curve analysis revealed that the percetage BRS increase had predictive value for the discrimination of responders and non-responders (area-under-the-curve 0.69; 95% confidence interval 0.51-0.87; maximal accuracy 0.70). Conclusions Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodelling. Key words: heart failure, baroreflex sensitivity, heart rate variability, cardiac resynchronization therapy.

J Clin Invest. 2009 Apr 20;
Ling H, Zhang T, Pereira L, Means CK, Cheng H, Gu Y, Dalton ND, Peterson KL, Chen J, Bers D, Heller Brown J

Ca2+/calmodulin-dependent kinase II (CaMKII) has been implicated in cardiac hypertrophy and heart failure. We generated mice in which the predominant cardiac isoform, CaMKIIdelta, was genetically deleted (KO mice), and found that these mice showed no gross baseline changes in ventricular structure or function. In WT and KO mice, transverse aortic constriction (TAC) induced comparable increases in relative heart weight, cell size, HDAC5 phosphorylation, and hypertrophic gene expression. Strikingly, while KO mice showed preserved hypertrophy after 6-week TAC, CaMKIIdelta deficiency significantly ameliorated phenotypic changes associated with the transition to heart failure, such as chamber dilation, ventricular dysfunction, lung edema, cardiac fibrosis, and apoptosis. The ratio of IP3R2 to ryanodine receptor 2 (RyR2) and the fraction of RyR2 phosphorylated at the CaMKII site increased significantly during development of heart failure in WT mice, but not KO mice, and this was associated with enhanced Ca2+ spark frequency only in WT mice. We suggest that CaMKIIdelta contributes to cardiac decompensation by enhancing RyR2-mediated sarcoplasmic reticulum Ca2+ leak and that attenuating CaMKIIdelta activation can limit the progression to heart failure.

Eur J Med Res. 2009 Mar 17; 14(3): 113-7
Fritzenwanger M, Lorenz F, Jung C, Fabris M, Thude H, Barz D, Figulla HR

BACKGROUND: Endothelial progenitor cells (EPC) which are characterised by the simulateous expression of CD34, CD133 and vascular endothelial growth receptor 2 (VEGF 2) are involved in the pathophysiology of congestive heart failure (CHF) and their number and function is reduced in CHF. But so far our knowledge about the number of circulating hematopoietic stem/ progenitor cells (CPC) expressing the early hematopoietic marker CD133 and CD34 in CHF is spares and therefore we determined their number and correlated them with New York Heart Association (NYHA) functional class. METHODS: CD34 and CD133 surface expression was quantified by flow cytometry in the peripheral venous blood of 41 healthy adults and 101 patients with various degrees of CHF. RESULTS: CD34+, CD133+ and CD34+/CD133+ cells correlated inversely with age. Both the number of CD34+ and of CD34+/CD133+ cells inversely correlated with NYHA functional class. The number of CD133+ cells was not affected by NYHA class. Furthermore the number of CD133+ cells did not differ between control and CHF patients. CONCLUSION: In CHF the release of CD34+, CD133+ and CD34+/CD133+ cells from the bone marrow seems to be regulated differently. Modulating the releasing process in CHF may be a tool in CHF treatment.

Curr Opin Cardiol. 2009 May; 24(3): 203-8Malhotra R, Mason PKPURPOSE OF REVIEW: Familial dilated cardiomyopathy is an underrecognized form of dilated cardiomyopathy. Lamin A/C deficiency is probably the most common cause of familial dilated cardiomyopathy. This review will focus on the emerging knowledge of epidemiology, diagnosis, and treatment of patients with lamin A/C deficiency, as well as possible disease mechanisms. RECENT FINDINGS: Screening of patients with dilated cardiomyopathy continues to indicate that lamin A/C deficiency is a significant cause. Multiple novel mutations have been found, suggesting that many mutations are limited to individuals or families. It is unknown how mutations cause the syndrome, although an animal model has shown that lamin A/C insufficiency causes apoptosis, particularly in the conduction system. Inheritance is predominantly autosomal dominant, but penetrance is variable. For symptomatic patients, the course is malignant, with conduction system disease, atrial fibrillation, heart failure, and sudden cardiac death. The data are contradictory, and currently, there is no clear marker for when a lamin A/C-deficient patient is at risk for sudden death. SUMMARY: Lamin A/C deficiency is an important cause of dilated cardiomyopathy, and diagnosis requires that clinicians have a high index of suspicion. Our knowledge of the mechanisms, diagnosis, and treatment of lamin A/C deficiency is incomplete. It is clear that patients with this condition have a malignant course and need to be followed aggressively.

J Am Med Inform Assoc. 2009 Apr 23; Zai AH, Farr K, Grant RW, Mort E, Ferris TG, Chueh HCOBJECTIVE We previously implemented an electronic heart failure registry at a large academic hospital to identify heart failure patients and to connect these patients with appropriate discharge services. Despite significant improvements in patient identification and connection rates, time to connection remained high, with an average delay of 3.2 days from the time patients were admitted to the time connections were made. Our objective for this current study was to determine the most effective solution to minimize time to connection. DESIGN We used a queuing theory model to simulate 3 different potential solutions to decrease the delay from patient identification to connection with discharge services. MEASUREMENTS The measures included average rate at which patients were being connected to the postdischarge heart failure services program, average number of patients in line, and average patient waiting time. RESULTS Using queuing theory model simulations, we were able to estimate for our current system the minimum rate at which patients need to be connected (262 patients/month), the ideal patient arrival rate (174 patients/month) and the maximal patient arrival rate that could be achieved by adding 1 extra nurse (348 patients/month). CONCLUSION Our modeling approach was instrumental in helping us characterize key process parameters and estimate the impact of adding staff on the time between identifying patients with heart failure and connecting them with appropriate discharge services.

Int J Emerg Med. 2008 Jun; 1(2): 107-11Wong E, Ng YYBACKGROUND: The patient with difficult airways is a common challenge for emergency physicians. AIMS: Our goal was to study the reasons for difficult airways in the emergency department. METHODS: We performed a prospective observational study of patients requiring advanced airway management from 1 January 2000 to 31 December 2006. RESULTS: There were 2,343 patients who received advanced airway management of which 93 (4.0%) were deemed difficult. The main diagnoses were cardiac arrest (28), trauma (27) and congestive heart failure (10). The main reasons for the difficult airways were attributed to an anterior larynx (38, 40.9%), neck immobility (22, 23.7%) as well as the presence of secretions and blood (14, 15.1%). The mean number of attempts at intubation was 3.6 versus 1.2 for all cases. The mortality rate of 40.5% among patients with difficult airways was not different from that of all patients who had airway management (41%). There were seven (0.3%) failed airways. Anaesthetists performed 21 (22.6%) of the rescue airways while surgeons performed 5 (5.4%). Of the rescue strategies performed, 24 were through the use of the bougie, 3 by cricothyroidotomy, 4 by tracheostomy, 6 with the GlideScope and 3 with the laryngeal mask airway. The rest the airways were secured by tracheal intubation using the laryngoscope. CONCLUSIONS: Emergency physicians manage most of the difficult airways successfully (68.8%). However, the success rate can be further improved through the more frequent use of the bougie or other rescue device. A possible suggestion would be for the emergency physician to use the bougie after the second or third attempt at direct orotracheal intubation.

Nephron Clin Pract. 2009 Apr 18; 112(2): c79-c85Brzosko S, Szkolka T, Mysliwiec MBackground/Aims: Impaired renal function is a strong risk factor for cardiovascular diseases and worsens a patient's prognosis. Renal dysfunction predicts mortality after acute stroke in the long term. On the other hand, in-hospital mortality after acute stroke is strongly associated with disorders of consciousness at the onset of stroke, severity of stroke, body temperature, blood sugar and some other comorbidities. The aim of the study was to analyze the possible role of renal dysfunction and/or signs of renal disease (proteinuria) on 30-day mortality after acute ischaemic stroke (AIS) based on the hospital medical records of one county. Methods: Medical records of 312 consecutive patients admitted to Ostrołeka County Hospital (Department of Neurology) between March 2000 and October 2002 for AIS were retrieved retrospectively to determine factors influencing 30-day survival. None of patients received thrombolytic therapy. Results: Among the patients analyzed, 74 (23.7%) died during the 30-day period. In a simple Cox proportional hazards regression model, negative predictive factors were: older age, higher pulse rate, lower estimated glomerular filtration rate (eGFR), proteinuria, elevated plasma glucose level, diabetes mellitus, atrial fibrillation and chronic heart failure. In a multivariate analysis, independent negative predictors of 30-day morbidity were: age hazard ratio (HR) 1.05 (95% CI 1.02-1.08), eGFR 100 mg/dl HR 2.96 (95% CI 2.22-3.70). Conclusion: The results of this study identify decreased eGFR and presence of dipstick proteinuria as a strong negative predictor of 30-day survival after AIS in patients not treated with thrombolytic agents.

Arq Bras Cardiol. 2009 Mar; 92(3): 173-9, 183-9Rienzo M, Saraiva JF, Nogueira PR, Gomes EP, Moretti MA, Ferreira JF, Armagnajian D, Mansur Ade P, Ramires JA, César LABACKGROUND: Patients (pts) with stable coronary artery disease (CAD) can benefit from a decrease in the blood pressure (BP), according to recent studies. OBJECTIVE: To evaluate the efficacy and tolerability of the fixed combination: amlodipine + enalapril, when compared to amlodipine in the normalization of the diastolic arterial pressure (DAP) ( or =90 and or =110 mmHg during the four-week wash-out with atenolol treatment alone, were excluded. After the wash-out, pts were randomly distributed for the use of the combination (A) or amlodipine (B) and were followed every four weeks up to 98 days. The initial doses (in mg) were, respectively: A- 2.5/10 and B- 2.5; the doses were increased when DAP > 85mmHg, at the visits. Statistical analysis was carried out with chi2, Fischer and analysis of variance, for p< 0.05. RESULTS: Of the 110 selected pts, 72 (A= 32, B= 40) were randomized. The decreases in DAP and systolic arterial pressure (SAP) were significant (p< 0.01), but with no difference between the groups in mmHg: SAP, A (127.7 +/- 13.4) and B (125.3 +/- 12.6) (p= 0.45) and DAP, A (74.5 +/- 6.7 mmHg) and B (75.5 +/- 6.7 mmHg) (p= 0.32). Group A presented a lower incidence of lower-limb edema: (7.1% vs 30.6%, p=0.02) on the 98th day of follow-up. CONCLUSION: The fixed combination of enalapril and amlodipine, as well as isolated amlodipine, was effective in the normalization of BP in pts with CAD and SAH stages I and II, adding blockage of the renin-angiotensin system.

J Cardiovasc Nurs. 2009 May-Jun; 24(3): 241-8Sloan RS, Pressler SJBACKGROUND: Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. OBJECTIVE: The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. METHODS: Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. RESULTS: The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. DISCUSSION: Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.

Arq Bras Cardiol. 2009 Mar; 92(3): 210-4, 222-6Arteaga E, de Araújo AQ, Bernstein M, Ramires FJ, Ianni BM, Fernandes F, Mady CBACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE: To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

Eur Heart J. 2009 Apr 23; Gewillig M, Brown SC, De Catte L, Debeer A, Eyskens B, Cossey V, Van Schoubroeck D, Van Hole C, Devlieger RAims The prevalence of intra-uterine ductal dysfunction is unknown and the clinical consequences are poorly understood. The aim of this study was to investigate the echocardiographic (ECHO) abnormalities and outcomes of this rare phenomenon. Methods and results Retrospective analysis of foetal (n = 602) and neonatal ECHO databases (n = 1477) between 1998 and 2007. Clinical and imaging studies were reviewed for pathology due to or associated with premature closure of the duct. Twelve cases were identified. Eight (1.3%) were diagnosed pre-natally at a median gestational age of 29.0 weeks (range: 20.0-37.5 weeks). Four neonates (0.3%) with significant cyanosis and absence of the arterial duct were also included. The most common ECHO features were: excessive right ventricular (RV) hypertrophy (100%), more than expected tricuspid and pulmonary regurgitation (100% and 92%, respectively), and right atrial dilation (75%). Premature induction of delivery was advised for five patients. Neonatal therapy consisted of observation and oxygen administration (n = 7), ventilation with pulmonary vasodilators (n = 5), and one required extracorporeal membrane oxygenation. There were three deaths due to respiratory failure with severe pulmonary hypertension. During follow-up, two children required additional right heart procedures and one developed a non-compaction cardiomyopathy. Conclusion Foetal premature closure of the arterial duct causes stress at different foetal ages and many different levels of the right heart and pulmonary circulation, resulting in a wide range of secondary pathology. Disproportionate RV hypertrophy is the most common finding. Clinical outcomes range from mild symptomatology to lethal respiratory insufficiency.

J Cardiovasc Nurs. 2009 May-Jun; 24(3): 207-15Evangelista LS, Heber D, Li Z, Bowerman S, Hamilton MA, Fonarow GCBACKGROUND: The effectiveness of high-protein (HP) diets in reducing body weight and adiposity and potentially improving clinical outcomes in heart failure (HF) is not known. OBJECTIVE: This feasibility study was conducted to evaluate the impact of 3 dietary interventions on body weight and adiposity, functional status, lipid profiles, glycemic control, and quality of life (QOL) in overweight and obese patients with HF and type 2 diabetes mellitus. DESIGN: Fourteen patients with HF with a body mass index greater than 27 kg/m2 were randomized to an HP diet, a standard protein diet, or a conventional diet. Data were obtained at baseline and 12 weeks. RESULTS: There were no significant differences in age (59 +/- 10 years), sex (78% male), New York Heart Association class (43% class II, 57% class III), and HF etiology or left ventricular ejection fraction (26 +/- 7) between the groups at baseline. Patients on the HP diet demonstrated significantly greater reductions in weight (P = .005), percent body fat (P = .036), total cholesterol (P = .016), triglyceride concentrations (P = .034), and low-density lipoprotein cholesterol (P = .041) and greater improvements in functional status (6-minute walk [P = .010] and VO2 peak [P = .003]), high-density lipoprotein cholesterol (P = .006), and physical QOL scores (P = .022) compared with those on standard protein and conventional diets. CONCLUSION: A 12-week HP diet resulted in moderate weight loss and reduced adiposity in a small sample of overweight and obese patients with HF that were associated with improvements in functional status, lipid profiles, glycemic control, and QOL. However, these preliminary findings must be confirmed in studies with more participants and long-term follow-up.

J Cardiovasc Nurs. 2009 May-Jun; 24(3): 192-7Stanek KM, Gunstad J, Paul RH, Poppas A, Jefferson AL, Sweet LH, Hoth KF, Haley AP, Forman DE, Cohen RABACKGROUND: Cardiovascular disease (CVD) and particularly heart failure (HF) have been associated with cognitive impairment in cross-sectional studies, but it is unclear how cognitive impairment progresses over time in older adults with these conditions. OBJECTIVE: The aim of this study was to prospectively examine cognitive function in patients with HF versus other forms of CVD. METHOD: Seventy-five older adults (aged 53-84 years) with CVD underwent Doppler echocardiogram to evaluate cardiac status and 2 administrations of the Dementia Rating Scale (DRS), a test of global cognitive functioning, 12 months apart. RESULTS: Although DRS performance did not statistically differ between groups at either administration, a significant between-group difference in the rate of cognitive change emerged (lambda = 0.87; F = 10.50; P = .002; omega 2 = 0.11). Follow-up analyses revealed that patients with HF improved significantly on global DRS performance, whereas patients with other forms of CVD remained stable. More specifically, patients with HF showed improvement on subscales of attention, initiation/perseveration, and conceptualization. Exploratory analyses indicated that higher diastolic blood pressure at baseline was associated with improved DRS performance in patients with HF (r = 0.38; P = .02). CONCLUSIONS: Patients with HF exhibited modest cognitive improvements during 12 months, particularly in attention and executive functioning. Higher diastolic blood pressure at baseline was associated with improvement. These results suggest that cognitive impairment in patients with HF may be modifiable and that improved blood pressure control may be an important contributor to improved function. Further prospective studies are needed to replicate results and determine underlying mechanisms.

J Am Med Inform Assoc. 2009 Apr 23; Azzam HC, Khalsa SS, Urbani R, Shah CV, Christie JD, Lanken PN, Fuchs BDOBJECTIVE We designed an automated electronic system that incorporates data from multiple hospital information systems to screen for acute lung injury (ALI) in mechanically ventilated patients. We evaluated the accuracy of this system in diagnosing ALI in a cohort of patients with major trauma, but excluding patients with congestive heart failure (CHF). DESIGN Single-center validation study. Arterial blood gas (ABG) data and chest radiograph (CXR) reports for a cohort of ICU patients with major trauma but excluding patients with CHF were screened prospectively for ALI requiring intubation by an automated electronic system. The system was compared to a reference standard established through consensus of two blinded physician reviewers who independently screened the same population for ALI using all available ABG data and CXR images. The system's performance was evaluated (1) by measuring the sensitivity and overall accuracy and (2) by measuring concordance with respect to the date of ALI identification (vs. reference standard). MEASUREMENTS One hundred ninety-nine trauma patients admitted to our level 1 trauma center with an initial Injury Severity Score (ISS) >/= 16 were evaluated for development of ALI in the first five days in an ICU after trauma. Main RESULTS The system demonstrated 87% sensitivity (95% confidence interval [CI] 82.3 to 91.7) and 89% specificity (95% CI 84.7 to 93.4). It identified ALI before or within the 24-hour period during which ALI was identified by the two reviewers in 87% of cases. CONCLUSIONS An automated electronic system that screens intubated ICU trauma patients, excluding patients with CHF, for ALI based on CXR reports and results of ABGs is sufficiently accurate to identify many early cases of ALI.

Hypertens Res. 2009 Apr 24; Fukui S, Fukumoto Y, Suzuki J, Saji K, Nawata J, Shinozaki T, Kagaya Y, Watanabe J, Shimokawa HDiabetes mellitus (DM) is a major risk factor for heart failure, independent of coronary artery disease or hypertension (HT). Therefore, our study was designed to examine the mechanisms of DM-induced left ventricular (LV) diastolic dysfunction. In this study, we made five different 10-week treatment groups of Dahl salt-sensitive rats as follows: Control; a low-salt (0.5% NaCl) diet, HT; a high-salt (5% NaCl) diet, DM; a low-salt diet with streptozotocin (STZ) injection (30 mg kg(-1) i.p.), HT+DM; a high-salt diet with STZ injection, and the Olmesartan group; a high-salt diet with STZ treated with an angiotensin receptor blocker, olmesartan (1 mg kg(-1) day(-1)). Cardiac diastolic dysfunction with a preserved systolic function was noted in the HT group, and was most prominently noted in the HT+DM group, characterized by enhanced cardiac fibrosis, whereas the extent of HT and myocardial hypertrophy was comparable between the two groups. Myocardial expressions of collagen III, transforming growth factor-beta2, angiotensin-converting enzyme (ACE), angiotensin II type-1 receptor and myocardial oxidative stress (evaluated by 4-hydroxy-2-nonenal-modified protein) were mostly enhanced in the HT+DM group. Importantly, there was a positive correlation between the extent of diastolic dysfunction and that of myocardial ACE expression. All these cardiac abnormalities induced by DM and HT were ameliorated in the olmesartan group. These results indicate that DM accelerates diastolic dysfunction in hypertensive heart disease through activation of the renin-angiotensin system, with subsequent inflammatory and oxidative stresses and myocardial fibrosis, suggesting that an inhibition of the system is effective for the treatment of diastolic dysfunction in this combined disorder.Hypertension Research advance online publication, 24 April 2009; doi:10.1038/hr.2009.43.

J Hypertens. 2009 Apr 17;
Volpe M, Tocci G, Sciarretta S, Verdecchia P, Trimarco B, Mancia G

OBJECTIVE: To evaluate the effects of treatments based on angiotensin II receptor blockers (ARBs) on the risk of myocardial infarction (MI), cardiovascular and all-cause death, as compared with conventional treatment or placebo. METHODS: We performed a meta-analysis of all available major international, randomized clinical trials (20 trials, n = 108 909 patients, mean age 66.5 +/- 4.1 years), published by 31 August 2008, comparing ARBs with other drugs or conventional therapies (placebo) and reporting MI incidence. RESULTS: During a mean follow-up of 3.3 +/- 1.1 years, a total of 2374/53 208 and 2354/53 153 cases of MI were recorded in ARB-based groups and in comparator arms, respectively [odds ratio (OR) 95% confidence interval (CI) 1.008 (0.950-1.069)]. Risks of MI were not different when tested in different clinical conditions, including hypertension, high cardiovascular risk, stroke, coronary disease, renal disease and heart failure. No significant differences in the risk of MI between treatment with ARBs versus placebo [OR 95% CI 0.944 (0.841-1.060)], beta-blockers and diuretics [OR 95% CI 0.970 (0.804-1.170)], calcium channel blockers [OR 95% CI 1.112 (0.971-1.272)], or angiotensin-converting enzyme (ACE) inhibitors [OR 95% CI 1.008 (0.926-1.099)] were observed. Analysis of trials comparing combination therapy based on ARBs plus ACE inhibitors versus active treatments or placebo showed equivalent MI risk [OR 95% CI 0.996 (0.896-1.107)]. CONCLUSION: The present meta-analysis indicates that the risk of MI is comparable with use of ARBs and other antihypertensive drugs in a wide range of clinical conditions.

Clin Exp Nephrol. 2009 Apr 21;
Rekik S, Trabelsi I, Hentati M, Hammami A, Jemaa MB, Hachicha J, Kammoun S

BACKGROUND: Infective endocarditis (IE) is a dreaded complication in hemodialysis (HD) patients and is strongly associated with morbidity and mortality. OBJECTIVES: Our aim was to investigate clinical and echocardiographic characteristics, microbiological profile, management and outcome of patients on HD in a Tunisian (Tunisia, North Africa) high-volume tertiary-care centre. METHODS: Among 182 patients who fulfilled the modified Duke criteria for infective endocarditis between January 1997 and December 2006, 16 were on chronic HD and were included in the study. RESULTS: Mean age was 52.5 +/- 22.3 years, ten were male and arteriovenous fistulas were the most commonly used access sites (12 out of 16 cases). Average duration of dialysis was 27.3 +/- 30 months. Major causative organisms were Staphylococcus species (including methicillin-resistant Staphylococcus aureus) in 11 (68.7%) of the 16 cases. The mitral valve was the most commonly affected [9 patients out of 16 (56.2%)], followed by aortic valve in 4 cases (25.0%) and tricuspid valve in 1 case (6.2%). Complications were frequent, including congestive heart failure (56.2%), secondary septic localisations (31.2%), arterial emboli (18.7%), and cerebral haemorrhage (6.2%). Five patients underwent surgery and seven died during hospitalization (43.7% mortality rate). No recurrences of IE were recorded in the nine survivors after average 21.7 +/- 17.3 months follow-up. CONCLUSION: In this largest reported confirmed IE series in dialysis patients in a developing country, mortality was very high; mitral valve was the most commonly affected valve. Staphylococcus species were the major causative organisms.

Eur J Heart Fail. 2009 Apr 19;
Krum H, Curtis SP, Kaur A, Wang H, Smugar SS, Weir MR, Laine L, Brater DC, Cannon CP

AIMS: Non-steroidal anti-inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors. METHODS AND RESULTS: We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59-12.47; P <0.0001), age >/=65 years (2.56, 1.65-3.98; P <0.0001), and history of hypertension (1.83, 1.16-2.89; P = 0.0094) or diabetes (1.83, 1.15-2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13-3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac. CONCLUSION: History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose-related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled. (Clinicaltrials.gov: NCT00092703, NCT00092742, NCT00250445).

Int J Emerg Med. 2008 Jun; 1(2): 91-5Johnson GG, Decker WW, Lobl JK, Laudon DA, Hess JJ, Lohse CM, Weaver AL, Goyal DG, Smars PA, Reeder GSBACKGROUND: Exercise treadmill testing (ETT) has been standard for evaluating outpatients at risk for cardiovascular events. Few studies have demonstrated its prognostic usefulness in emergency department chest pain units or have used the Duke score [(exercise duration in minutes) - (5 x ST-segment deviation in millimeters) - (4 x treadmill angina index)] to grade its performance. AIMS: Our objective was to assess the usefulness of this score in a chest pain unit to predict cardiovascular events. METHODS: From November 2000 to October 2001, we retrospectively studied consecutive patients in the chest pain unit. Those undergoing ETT were stratified into "low" (Duke score >/= 5) and "moderate/high" risk groups (< 5). Cardiovascular events defined as death, myocardial infarction > 24 h after presentation, revascularization, acute congestive heart failure, stroke or arrhythmia were identified within 1 year after presentation. Differences in risk of having a cardiovascular event among low-risk and moderate/high-risk groups are presented. RESULTS: During the study period, 1,048 patients entered the chest pain unit; 800 met inclusion criteria. Of these, 599 received ETT and 201 had contraindications or a positive finding in the chest pain unit protocol before ETT. Cardiovascular event rates were 0.7% (3/454), 15.2% (22/145) and 14.9% (30/201) after 1 month of follow-up for low-risk, moderate/high-risk and no-ETT groups, respectively. CONCLUSIONS: According to the Duke score, the low-risk group developed minimal cardiovascular events compared with the moderate/high-risk group. The Duke score appears effective for risk stratification of chest pain patients in chest pain units.

Eur Heart J. 2009 Apr 21; Anker SD, Voors A, Okonko D, Clark AL, James MK, von Haehling S, Kjekshus J, Ponikowski P, Dickstein K, Aims The prevalence, incidence, and prognostic value of anaemia in patients with an acute myocardial infarction (AMI) complicated by heart failure is unclear. Methods and results We analysed the relationship between haemoglobin (Hb) and outcome in 5010 patients with AMI complicated by heart failure in the OPTIMAAL study. In 3921 patients, follow-up Hb levels were available at 365 (+/-90) days. In a subgroup of 224 patients, iron-related haematinics were assessed at baseline and during follow-up. At baseline, mean Hb was 12.6 +/- 1.3 g/dL in women and 13.7 +/- 1.4 g/dL in men. Hb < 11.5 g/dL was found in 9.3% of patients (women: 18.2%, men: 5.8%). Lower haemoglobin at baseline was clearly associated with female gender and the presence of diabetes, higher age and Killip class, lower body mass index, systolic blood pressure, total cholesterol, and the absence of current smoking (all P < 0.05). Higher Hb [per one standard deviation (SD)] related to lower mortality [adjusted hazard ratios (HR) 0.88; 95% confidence interval (CI) 0.83-0.93], CHF hospitalizations [HR 0.85 (0.77-0.93)], and all-cause hospitalizations [HR 0.96 (0.92-0.99), all P < 0.05]. In patients without anaemia at baseline, the anaemia incidence after 1 year of follow-up was 10.1% in women and 10.0% in men. Of patients with anaemia at baseline, 65% did not have anaemia at 12 months and 46% did not have anaemia at any time during follow-up (median 3.0 years, inter-quartile range, Q1-Q3 = 2.7-3.3 years). At 12 months, an increase in Hb (per SD) was related to lower mortality [HR 0.73 (0.63-0.85; P < 0.0001)] independent of baseline Hb and other clinical characteristics. Conclusion In patients with complicated AMIs, anaemia on admission and/or reductions in haemoglobin during follow-up are independent risk factors for mortality and hospitalization. Studies are warranted to determine whether correcting anaemia after a complicated AMI improves outcome.

Cardiol Young. 2009 Apr 22; Fesslova V, Vignati G, Brucato A, De Sanctis M, Butera G, Pia Pisoni M, Chiappa E, Acaia B, Meroni PLOBJECTIVES: to analyse retrospectively the data of fetuses diagnosed with isolated complete atrioventricular block and efficacy of treatment of the fetus by maternal therapy.MaterialsBetween 1992 and 2004, we diagnosed complete atrioventricular block in 26 singleton and 2 twins fetuses of 27 pregnant women known to have anti Ro/La antibodies, 11 with autoimmune disease, one patient analysed in 2 pregnancies. At presentation, 20 of the fetuses were compensated and non-hydropic, while 8 had hydrops. Twenty patients were treated with dexamethasone, 2 with associated salbutamol and one mother with isoproterenol. RESULTS: Age at presentation was not different between the hydropic and non-hydropic fetuses. The fetuses with hydrops, however, had a lower mean heart rate at presentation, 48.5 +/- 9.25 with a range from 32 to 60, compared to 59.95 +/- 7.9 beats per minute, with a range from 50 to 80, in the non-hydropic fetuses (p less than 0.002). Equally, after birth the mean heart rate in hydropic fetuses was 42.6 +/- 5.1, with a range from 38 to50, as opposed to 56.05 +/- 11.8 beats per minute, with a range from 29 to 110, in the non-hydropic fetuses (p less than 0.015), The hydropic fetuses were delivered at 31.7 +/- 3.8 weeks' gestation, with a range from 29 to 38 weeks (p less than 0.003) compared to 35.5 weeks' gestation +/-2.04, with a range from 31 to 38, in the non-hydropic fetuses. Mortality was 37.5% in the hydropic fetuses, versus 5% of those without hydrops (p less than 0.02). Pacemakers were implanted in 22 of 26 infants born alive, at a median of 45 days, with a range from 1 day to 5 years, in those without hydrops during fetal life, and 3 days, with a range from 1 day to 8 months in those afflicted by hydrops, of whom 2 died despite the implant of the pacemaker. The presence and degree of hydrops had a significantly negative predictive value. No significant differences were observed between the treated and non treated cases, albeit that administration of steroids ameliorated rapidly the hydrops in 3 of 5 cases. CONCLUSIONS: The outcome in our cases was mainly dependent on the presence and degree of fetal cardiac failure. Treatment of the fetus by maternal administration of steroids did not result in any regression of the conduction disorder, but had a favourable effect on fetal hydrops.

Crit Care Med. 2009 Apr 20; Richir MC, van Lambalgen AA, Teerlink T, Wisselink W, Bloemena E, Prins HA, de Vries TP, van Leeuwen PAOBJECTIVE:: Both arginine and asymmetric dimethylarginine (ADMA) play a crucial role in the arginine-nitric oxide pathway. Low arginine and high ADMA levels can be found in critically ill patients after major surgery. The aim of this study was to evaluate the effects of low arginine plasma concentrations in combination with high ADMA plasma concentrations on hemodynamics and organ blood flow. DESIGN:: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS:: Male Wistar rats (n = 21), anesthetized. INTERVENTIONS:: Rats were randomly assigned to three groups: a control group, an ADMA group, or an arginase (ASE)/ADMA group. In the control group, rats received (at t = 0) an intravenous (IV) infusion of 1.5 mL 0.9% NaCl during a 20-minute period. After 60 minutes (t = 60), rats received an IV bolus of 1.0 mL 0.9% NaCl. In the ADMA group, rats received an IV infusion of 1.5 mL 0.9% NaCl during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). In the ASE/ADMA group, rats received an IV infusion of 1.5 mL ASE (3200 IU) solution during a 20-minute period and at t = 60 an IV bolus of 1.0 mL ADMA (20 mg/kg). MEASUREMENTS AND MAIN RESULTS:: Infusion of ADMA (20 mg/kg) and ASE (3200 IU) resulted in increased plasma ADMA levels and decreased arginine levels. During the whole experiment, systemic hemodynamics (heart rate, mean arterial pressure [MAP], and cardiac output) were measured. In addition, organ blood flow was measured at t = 90 and t = 180 minutes, using fluorescent microspheres. Compared with the control group, MAP and systemic vascular resistance were increased after infusion of ADMA. Infusion of ASE in combination with ADMA significantly deteriorated systemic hemodynamics (MAP, cardiac output, stroke volume, and systemic vascular resistance) and organ blood flow through the kidney and spleen. In addition, an initial decrease in arterial flow, followed by a later major increase, and panlobular apoptosis and necrosis of the liver was observed. CONCLUSIONS:: The current study shows that low arginine plasma levels in combination with high ADMA plasma levels deteriorates systemic hemodynamics and reduces blood flow through the kidney and spleen and liver. These data suggest that a diminished nitric oxide production may be involved in the onset of organ failure.

Eur J Med Res. 2009 Mar 17; 14(3): 106-12
Heringlake M, Kox T, Poeling J, Klaus S, Hanke T, Franz N, Eberhardt F, Heinze H, Armbruster FP, Bahlmann L

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.

Eur J Appl Physiol. 2009 Apr 18;
Morris NR, Snyder EM, Beck KC, Johnson BD

Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 +/- 14 year, resting ejection fraction = 23 +/- 8%) and control subjects (51 +/- 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C(2)H(2) washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 +/- 8.2 s, Q = 4.3 +/- 1.1 l min(-1); control: LLCT = 55.3 +/- 10.9 s, Q = 4.5 +/- 0.5 l min(-1)) to peak exercise (HF:LLCT = 20.6 +/- 3.9* s, Q = 8.8 +/- 2.5* l min(-1); control:LLCT = 14.9 +/- 2.4 s, Q = 16.5 +/- 1.2 l min(-1); *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.