Search

Current cardiovascular pharmacotherapy targets maladaptive overactivation of the renin-angiotensin-aldosterone system (RAAS), which occurs throughout the continuum of cardiovascular disease spanning from hypertension to heart failure with reduced ejection fraction. Over the past 16 years, 4 prospective, randomized, placebo-controlled clinical trials using candesartan, perindopril, irbesartan, and spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) failed to demonstrate increased efficacy of RAAS blockade added to guideline-directed medical therapy. We reappraise these trials and their weaknesses, which precluded statistically significant findings. Recently, dual-acting RAAS blockade with sacubitril-valsartan relative to stand-alone valsartan failed to improve outcome in the PARAGON-HF trial (Efficacy and Safety of LCZ696 Compared with Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction). The majority of patients with HFpEF experience hypertension, frequently with subclinical left ventricular dysfunction, contributed to by comorbidities such as coronary disease, diabetes mellitus, overweight, and atrial fibrillation. Contrasting the findings in HFpEF, trials evaluating RAAS blockade on either side of HFpEF on the cardiovascular continuum in patients with high-risk hypertension and heart failure with reduced ejection fraction, respectively, showed positive outcomes. We do not have a biologically plausible explanation for such divergent efficacy of RAAS blockade. Based on considerations of well-established clinical efficacy in hypertension and heart failure with reduced ejection fraction and the shortcomings of aforementioned clinical trials in HFpEF, we argue that RAAS blockers including MRAs (mineralocorticoid receptor antagonists; aldosterone antagonists) should be used in the treatment of patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical condition. Initially called diastolic heart failure, it soon became clear that this condition is more than the opposite side of systolic heart failure. It is increasingly prevalent and lethal. Currently, HFpEF represents more than 50% of heart failure cases and shares a 90-day mortality and readmission rate similar to heart failure with reduced ejection fraction. Heart failure with preserved ejection fraction is best considered to be a systemic disease. From a cardiovascular standpoint, it is not just a stiff ventricle. A stiff ventricle combined with a stiff arterial and venous system account for the clinical manifestations of flash pulmonary edema and the marked changes in renal function or systemic blood pressure with minor changes in fluid volume status. No effective pharmacologic treatments are avail able for patients with HFpEF, but an approach to the musculoskeletal system has merit: the functional limitations and exercise intolerance that patients experience are largely due to abnormalities of peripheral vascular function and skeletal muscle dysfunction. Regular exercise training has strong objective evidence to support its use to improve quality of life and functional capacity for patients with HFpEF. This clinical review summarizes the current evidence on the pathophysiologic aspects, diagnosis, and management of HFpEF.

Hypertension, untreated or insufficiently treated, is the most important cause of left ventricular hypertrophy, coronary heart disease, myocardial infarction, arrhythmias, and eventually cardiac failure whether left ventricular ejection fraction is reduced or preserved. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists (aldosterone antagonists) are cornerstones in the treatment of both patients with heart failure with reduced ejection fraction and high-risk hypertension as these drug classes lower morbidity and mortality. These drugs as well as calcium antagonists can safely be used in patients with preserved ejection fraction though no drug class has been shown specifically to lower mortality. Diuretic treatment is generally considered a symptomatic treatment in heart failure patients but is needed in high-risk hypertension to control the high blood pressure and prevent complications. However, for primary prevention of heart failure in hypertensive patients, the various drug classes appear equally effective.

Background Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA. Methods Patients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality. Results SUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03–1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24–2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89–1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539). Conclusions High SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Objectives The aim of this study was to evaluate the prognostic impact of anemia in outpatients with chronic heart failure attending specialized heart failure clinics and specifically to investigate its prognostic utility in patients with severe renal dysfunction or advanced heart failure. Background Anemia is an independent prognostic marker in patients with heart failure. The effect of anemia on mortality decreases with increasing creatinine levels. Methods Multivariate Cox regression analyses were used to investigate the prognostic effect of anemia in 4,144 patients with heart failure from 21 outpatient heart failure clinics in Norway. Severe renal failure was defined as estimated glomerular filtration rate ≤45 ml/min/1.73 m 2 and advanced heart failure as New York Heart Association functional classes IIIb and IV. Results Baseline anemia was present in 24% and was a strong predictor of all-cause mortality (adjusted hazard ratio [HR]: 1.30, 95% CI: 1.09 to 1.56, p = 0.004). Baseline anemia did not predict mortality in the 752 patients with severe renal dysfunction (adjusted HR: 1.08, 95 % CI: 0.77 to 1.51, p = 0.662) and the 528 patients with advanced heart failure (adjusted HR: 0.87, 95% CI: 0.56 to 1.34, p = 0.542). In the 1,743 patients who attended subsequent visits, sustained anemia independently predicted worse prognosis (adjusted HR: 1.47, 95% CI: 1.10 to 1.94, p = 0.008), whereas transient and new-onset anemia did not. Conclusions According to our study, baseline anemia was not an independent predictor of all-cause mortality in outpatients with heart failure and accompanied severe renal dysfunction or advanced heart disease. Sustained anemia after optimizing heart failure treatment might imply worse prognosis independently of renal function and New York Heart Association functional class.

Hospitalization rates, morbidity and mortality are undesirably high in heart failure (HF) patients. An organized system of HF specialist outpatient care has been recommended, but the best way to implement such programmes is not clearly established.To evaluate HF patient characteristics, management and outcome in outpatient HF clinics.Data from HF patients at 24 hospital outpatient clinics were entered in a common database allowing each centre to monitor its own practice against the rest.A total of 3632 patients were included. At the last registered visit, ACE inhibitors or angiotensin receptor blockers were prescribed for 87%; beta blockers, 83%; spironolactone, 33% and loop diuretics 87% of the patients. The number of hospital admissions and days stayed in hospital for cardiovascular reasons were significantly reduced (p0.001). Mortality was high, 11.5 and 22% after one and two years, respectively.The use of evidence-based medication increased over time in HF clinics with the ability of the individual clinics to compare their treatment to other sites. Thus, establishment of specialized HF clinics managed in a registry network might improve the quality of care.

Background The aim of this study was to relate levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, L-arginine, the substrate for NO generation, and radical oxygen species (ROS) formation to severity of chronic heart failure. The effect of 4 months’ group-based exercise training was further investigated. Method and Results Eighty patients, aged 45-85 years with New York Heart Association (NYHA) functional class II-IIIb, all on optimal medical treatment, were included. A 6-minute walking test and a bicycle exercise test were performed, and fasting blood samples were collected for determination of N-terminal pro–brain natriuretic peptide (NT-proBNP), L-arginine, ADMA, and ROS generation in circulating leukocytes. ADMA levels were significantly higher in patients in NYHA functional class III versus II ( P = .024), and the L-arginine–ADMA ratio was significantly lower ( P = .005). After adjustment for covariates, L-arginine–ADMA ratio was associated with 6-minute walking distance ( P = .004), exercise capacity ( P = .026), and inversely with NT-proBNP ( P = .015). Stimulated levels of peroxynitrite on monocytes were inversely related to left ventricular ejection fraction ( P = .005). No effect of 4 weeks’ exercise training on the measured variables was obtained. Conclusions The strong relationship seen between L-arginine–ADMA ratio, ROS formation in leukocytes, and severity of chronic heart failure contributes to increased knowledge of endothelial dysfunction related to the NO pathway in such patients.

Impaired renal function confers an adverse prognosis in patients with heart failure (HF). The aims of the present study were to identify factors associated with and predictive of impaired renal function and to assess the relationship between estimated glomerular filtration rate (eGFR) and all-cause mortality in outpatients with HF.Baseline data on 3605 patients (median age 73 years, 70.1% men) from 24 outpatient HF clinics in Norway were analyzed. Median follow-up time was 9 months. Renal dysfunction (eGFR60 mL/min) was present in 44.9%. The population was randomized into equal-sized model-building and validation samples to enhance model stability. eGFR was an independent predictor of all-cause mortality (HR 0.94 per 5 mL/min increase, P = .001). Use of spironolactone (P = .002), higher blood pressure (P.001), and lower hemoglobin levels (P = .002) were predictors of impaired renal function. Increasing doses of loop diuretics were strongly associated with eGFR at baseline (P.001), but only tended to predict worsening renal function during follow-up (P = .08).Clinically significant reduction in renal function was prevalent in outpatients with HF, and was a strong predictor of all-cause mortality. Use of loop diuretics and spironolactone should be carefully evaluated as these agents may adversely affect renal function.

Hypertension may affect the diagnostic performance of B-type natriuretic peptide (BNP). The objective of the present study was to assess the impact of a history of hypertension or blood pressure elevation on admission on the diagnostic performance of BNP in the diagnosis of heart failure (HF) in patients with acute dyspnea. BNP levels were measured using a rapid point-of-care device in 1,586 patients with acute dyspnea. In patients with HF, BNP levels did not differ between those with and without histories of hypertension. Conversely, in patients without HF, a history of hypertension was associated with higher median BNP levels (38 pg/ml [interquartile range 13 to 119] vs 21 pg/ml [interquartile range 7 to 64], p

An exaggerated, early prolactin response (p less than 0.01) was observed in ten patients with untreated essential hypertension (148 +/- 4/97 +/- 1 mmHg, means +/- SE) compared with ten healthy normotensive men of the same age (124 +/- 3/78 +/- 2 mmHg) after administration of metoclopramide, a competitive dopamine antagonist. The normotensive peak value of prolactin never exceeded that of the hypertensive (p less than 0.05). Since prolactin is considered an indicator of central dopaminergic activity, these findings suggest an altered central dopaminergic activity in mild essential hypertension.

Seventeen 50-year-old hypertensive men (157 +/- 4/110 +/- 2 mmHg, mean +/- SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4 +/- 1.7 ng/l (0.05 less than p less than 0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p less than 0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p less than 0.001) and plasma dopamine showed an increase by 58% (p less than 0.001). Plasma renin concentration increased four-fold during sodium depletion (p less than 0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5 +/- 4.0 ng/l (p less than 0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143 +/- 3/103 +/- 2 mmHg, p less than 0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.

Hypertensive men aged 42 (n = 35) were compared to normotensive men of similar age (n = 44). Platelet numbers were similar in the two groups, but hypertensive men had larger venous platelets than the normotensive (7.46 versus 7.12 femtoliter, p = 0.01). Plasma concentration of beta-thromboglobulin (BTG), a marker of platelet release reaction, was increased in arterial blood in hypertension (40 versus 21 micrograms/l, p = 0.02). The normotensive subjects had markedly higher BTG concentration in venous compared to arterial blood (p less than 0.01), but this arterio-venous difference was not present in the hypertensive group. Twelve normotensive subjects received infused saline, which did not induce changes in platelet variables. Adrenaline was infused to 13 hypertensive and 12 normotensive subjects, with dose gradually increasing to 0.04 microgram/kg/min. Platelet count increased in both groups, but significantly more in the hypertensive group. Platelet volume and BTG both increased markedly in the hypertensive group, but not in the normotensive men. Thus, young men with hypertension have increased platelet activity and increased sensitivity to exogenous adrenaline.

The long-term effects of prazosin in chronic congestive heart failure were studied in 10 patients (New York Heart Association class III-IV) in a double-blind cross-over study. Patients with systolic blood pressure greater than 120 mmHg and left ventricular filling pressure greater than 15 mmHg were included. Prazosin lowered the arteriovenous oxygen difference both at rest and during exercise (p less than 0.05), increased cardiac index (p less than 0.01) and reduced right atrial pressure and systemic vascular resistance (p less than 0.05) during exercise. Left ventricular filling pressure was also reduced, but not significantly, during exercise. Our data show that prazosin has beneficial long-term effects during exercise in patients with chronic congestive heart failure.

Studies on the long-term effects of exercise training programs on functional capacity and the quality of life in patients with chronic heart failure (CHF) are sparse. The aim of this study was to evaluate the long-term effects of group-based, high-intensity interval training on functional capacity and the quality of life in 80 patients with stable CHF (mean age 70.1 +/- 7.9 years) in New York Heart Association classes II to IIIB. Patients were randomized to either an exercise group (n = 40) or a control group (n = 40). The mean ejection fractions at baseline were 31 +/- 8% in the exercise group and 31 +/- 1% in the control group. The exercise group exercised twice a week for 4 months in addition to 4 consultations with a CHF nurse. Six-minute walking distance, workload and exercise time on a cycle ergometer test, and the quality of life were measured at baseline and 4 and 12 months after enrollment. After 4 months, functional capacity (6-minute walking distance +58 vs -15 m, p0.001) and the quality of life (Minnesota Living With Heart Failure Questionnaire score +10 vs -1 point, p0.005) improved significantly in the exercise group compared with the control group. After 12 months, the improvements were still significant in the exercise group compared with the control group for all parameters (6-minute walking distance +41 vs -20 m, p0.001; workload +10 vs -1 W, p = 0.001; exercise time +53 vs -6 seconds, p = 0.003; quality of life +10 vs -6 points, p = 0.003). In conclusion, the results support the implementation of a group-based aerobic interval training program to improve long-term effects on functional capacity and the quality of life in patients with CHF.

The sympathetic nervous system is implicated in the development and maintenance of hypertension. However, the predictive impact of arterial plasma catecholamines has never been reported. We investigated arterial catecholamines and blood pressures (BPs) prospectively over 20 years in a group of well-characterized middle-aged men.Fifty-six of original 79 men were available for the follow-up. Multiple regression analysis was done with mean BP at follow-up as a dependent variable, and arterial plasma catecholamines and BP at baseline as independent variables.Half of the originally normotensive men developed hypertension during follow-up. There were significant differences in the screening BP values measured at baseline between the new hypertensives and the sustained normotensives. Multiple regression analysis revealed arterial adrenaline at baseline as an independent predictor of mean BP at follow-up in the new hypertensives (beta = 0.646, R2 = 0.42, p = 0.007). Furthermore, arterial noradrenaline at baseline was a negative independent predictor of mean BP at follow-up in the sustained normotensives (beta = -0.578, R2 = 0.334, p = 0.020). Noradrenaline increased with age in the group as a whole (1318+/-373 vs 1534+/-505 pmol/l, p = 0.010) while adrenaline did not change.Our data suggest that arterial adrenaline is involved in the development of hypertension over 20 years in middle-aged men. Men with sustained normotension may have an inherent protection against sympathetic overactivity. Furthermore, screening BP at baseline in normotensive men differentiated between those who developed hypertension and those who remained normotensive at follow-up.

Oxidative stress might exert deleterious cardiovascular effects. The aim of the present study was to compare the antioxidative effects of carvedilol and atenolol. Levels of oxidized low-density lipoprotein cholesterol (ox-LDL), vitamin E, and thiobarbituric acid reactive substances (TBARS) were measured. In a prospective, open, and end-point-blinded study, 232 patients with an acute myocardial infarction (AMI) were randomized to receive either carvedilol or atenolol at equipotent doses, and the previously mentioned 3 parameters were measured at baseline and after 12 months of active treatment, with changes during the study period being compared both within and between the groups. Ox-LDL decreased in both treatment modalities, from 40.5 +/- 15.6 to 35.0 +/- 13.8 U/L, P = 0.0001, in the carvedilol group and from 40.3 +/- 16.5 to 37.4 +/- 13.1 U/L, P = 0.044, in the atenolol group, with a significant between-group difference in the changes (P = 0.036). The levels of vitamin E did not change during carvedilol treatment (31.0 +/- 10.2 vs 31.7 +/- 11.1 micromol/L), but it decreased marginally in the atenolol group (30.8 +/- 12.1 vs 27.2 +/- 9.1 micromol/L, P = 0.056), with a significant between-group difference (P = 0.008). No significant change in TBARS was observed between the carvedilol and atenolol groups (P = 0.454). These results indicate that carvedilol has a more pronounced antioxidative effect than atenolol in post-AMI patients, which might be of clinical importance.

Background B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP ≥100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. Methods The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. Results Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively ( P Conclusions Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP ≥54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP ≥170 pg/mL) could be used to increase specificity.

Increased sympathetic activity may be an underlying mechanism in cardiovascular disease. It has been hypothesized that the degree of left ventricular (LV) hypertrophy is partly related to the blood pressure level, and partly to neurohormonal factors. The aim of this study was to investigate predictors of LV mass, including arterial plasma noradrenaline as an index of sympathetic activity, with particular emphasis on subjects who developed hypertension over a period of 20 years.In a 20-year prospective study of middle-aged men, sustained hypertensives (n = 22), new hypertensives (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were examined both at baseline and after 20 years of follow-up (at ages 42.1 +/- 0.5 and 62.3 +/- 0.6 years, respectively). Relationships between arterial plasma catecholamines, blood pressure and body mass index at baseline to left ventricular parameters by echocardiography at follow-up were investigated.Groups were homogeneous regarding age, gender, race and body build. The group of sustained hypertensives had significantly more LV hypertrophy (P = 0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043) and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (beta = 0.47) was found to predict LV mass index after 20 years independently of BMI (beta = 0.45) and SBP (beta = 0.22) at baseline (R adjusted = 0.345, P = 0.037). Such a relationship was not found in the controls or in the sustained hypertensives, of which 16 were treated with antihypertensive drugs.Arterial plasma noradrenaline at baseline, as an index of sympathetic activity, predicts LV mass at follow-up independently of systolic blood pressure and body build in middle-aged men who developed hypertension over a period of 20 years.

We examined the relation between B-type natriuretic peptide (BNP) levels and a history of stable angina pectoris and/or healed myocardial infarction in 1,240 patients who were evaluated in the emergency department for possible heart failure. In patients who had heart failure, there was no relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction. However, in patients who did not have heart failure, there was a relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction but no significant independent relation in multiple regression analysis.

Objectives This study was designed to assess the diagnostic performance of B-type natriuretic peptide (BNP) in the diagnosis of acute congestive heart failure (CHF) in patients with permanent/paroxysmal atrial fibrillation (AF) presenting with acute dyspnea. Background It is unknown to what extent AF affects the diagnostic performance of BNP in patients presenting with acute dyspnea. Methods We studied 1,431 patients drawn from a cohort of patients (n = 1,586) with acute dyspnea who had BNP levels measured on arrival. Patients were prospectively classified according to the presence or absence of permanent/paroxysmal AF. Results In total, 292 patients had permanent/paroxysmal AF. In patients without HF, permanent/paroxysmal AF was associated with significantly higher BNP levels (p = 0.001). Conversely, in patients with HF, BNP levels did not differ significantly between patients with and without AF (p = 0.533). A BNP cutoff value of 100 pg/ml had a specificity of 40% and 79% for the diagnosis of acute HF in patients with and without AF, respectively. The areas under the receiver-operating characteristic curves were 0.84 (95% confidence interval 0.78 to 0.89) and 0.91 (95% confidence interval 0.89 to 0.93) for patients with and without AF, respectively. Conclusions In patients without, but not in those with HF, the presence of AF is associated with higher circulating BNP levels, suggesting that a higher diagnostic threshold should be used in patients with AF.

Background: β-Blockers have been found to reduce mortality and morbidity in postmyocardial infarction patients. However, it is not fully understood whether all β-blockers have similar favourable cardiovascular effects. The aim of this study was to compare the effects of carvedilol and atenolol on global and regional left ventricular ejection fraction (LVEF) and on predefined cardiovascular endpoints. Methods: In a single-centre, randomized, open, endpoint-blinded, parallel group study, 232 patients with acute myocardial infarction were randomized to treatment with carvedilol or atenolol. LVEF was measured by gated blood pool scintigraphy during the first week and after 12 months. The treatment was given orally within 24 h. The mean dose was 36.2 and 72.1 mg in the carvedilol and atenolol groups, respectively. Results: No significant difference was found between the two study groups in the mean global and regional LVEF. There tended to be fewer first serious cardiovascular events in the carvedilol compared with the atenolol group (RR = 0.83, 95% CI 0.56–1.23, p = 0.39). Cold hands and feet were observed less frequently in the carvedilol group (20 vs. 33%, p = 0.025). Conclusion: In patients following an acute myocardial infarction, no difference in either global or regional LVEF was observed between baseline and 12 months when treatment with carvedilol was compared with atenolol.

B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension.The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information.Significant differences in CHF rates were found on the basis of age (P.001) and racial group (P =.020) but not sex (P =.424). BNP levels increased with increasing age (P.001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic variables with log(10) BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false-negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points100 pg/mL.If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity.

Background: B-type natriuretic peptide (BNP) measurements are useful for diagnosing congestive heart failure (CHF) in patients presenting to the Emergency Department with acute dyspnoe. Whether the diagnostic accuracy of BNP is affected by the age and gender of the patients remains unknown. Aims: To evaluate the accuracy of BNP testing for diagnosing CHF in an unselected group of patients admitted to the emergency department of a Norwegian teaching hospital with a principal complaint of shortness of breath and to assess whether the diagnostic accuracy of the test differs according to age and gender. Methods: BNP levels in plasma were determined by a point-of-care device upon arrival in 155 patients presenting with acute dyspnoe. The diagnostic ‘gold’ standard for CHF was adjudicated by two independent cardiologists who were blinded to the BNP data. Results: By univariate logistic regression analysis, BNP was strongly related to a diagnosis of CHF. In a multivariate model BNP provided additional prognostic information to patient age and gender, radiographic evidence of pulmonary congestion and cardiomegaly, and the presence of pulmonary rales and jugular vein distention by physical examination. There was no significant interaction between age and BNP or between gender and BNP with regard to the accuracy of diagnosing CHF. The area under the receiver–operating characteristics-curve was 0.86 (95% confidence interval 0.78–0.93) in women and 0.90 (0.82–0.97) in men. The area under the curves were 0.82 (0.73–0.92) and 0.88 (0.80–0.97) for patients (both genders) aged ≥76 and

OBJECTIVES This study examines B-type natriuretic peptide (BNP) levels in patients with systolic versus non-systolic dysfunction presenting with shortness of breath. BACKGROUND Preserved systolic function is increasingly common in patients presenting with symptoms of congestive heart failure (CHF) but is still difficult to diagnose. METHODS The Breathing Not Properly Multinational Study was a seven-center, prospective study of 1,586 patients who presented with acute dyspnea and had BNP measured upon arrival. A subset of 452 patients with a final adjudicated diagnosis of CHF who underwent echocardiography within 30 days of their visit to the emergency department (ED) were evaluated. An ejection fraction of greater than 45% was defined as non-systolic CHF. RESULTS Of the 452 patients with a final diagnosis of CHF, 165 (36.5%) had preserved left ventricular function on echocardiography, whereas 287 (63.5%) had systolic dysfunction. Patients with non-systolic heart failure (NS-CHF) had significantly lower BNP levels than those with systolic heart failure (S-CHF) (413 pg/ml vs. 821 pg/ml, p < 0.001). As the severity of heart failure worsened by New York Heart Association class, the percentage of S-CHF increased, whereas the percentage of NS-CHF decreased. When patients with NS-CHF were compared with patients without CHF (n = 770), a BNP value of 100 pg/ml had a sensitivity of 86%, a negative predictive value of 96%, and an accuracy of 75% for detecting abnormal diastolic dysfunction. Using Logistic regression to differentiate S-CHF from NS-CHF, BNP entered first as the strongest predictor followed by oxygen saturation, history of myocardial infarction, and heart rate. CONCLUSIONS We conclude that NS-CHF is common in the setting of the ED and that differentiating NS-CHF from S-CHF is difficult in this setting using traditional parameters. Whereas BNP add modest discriminatory value in differentiating NS-CHF from S-CHF, its major role is still the separation of patients with CHF from those without CHF.

B-type natriuretic peptide is released from the cardiac ventricles in response to increased wall tension.We conducted a prospective study of 1586 patients who came to the emergency department with acute dyspnea and whose B-type natriuretic peptide was measured with a bedside assay. The clinical diagnosis of congestive heart failure was adjudicated by two independent cardiologists, who were blinded to the results of the B-type natriuretic peptide assay.The final diagnosis was dyspnea due to congestive heart failure in 744 patients (47 percent), dyspnea due to noncardiac causes in 72 patients with a history of left ventricular dysfunction (5 percent), and no finding of congestive heart failure in 770 patients (49 percent). B-type natriuretic peptide levels by themselves were more accurate than any historical or physical findings or laboratory values in identifying congestive heart failure as the cause of dyspnea. The diagnostic accuracy of B-type natriuretic peptide at a cutoff of 100 pg per milliliter was 83.4 percent. The negative predictive value of B-type natriuretic peptide at levels of less than 50 pg per milliliter was 96 percent. In multiple logistic-regression analysis, measurements of B-type natriuretic peptide added significant independent predictive power to other clinical variables in models predicting which patients had congestive heart failure.Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide is useful in establishing or excluding the diagnosis of congestive heart failure in patients with acute dyspnea.

Objective: The objective was to evaluate the effect of hormone replacement therapy (HRT) on plasma homocysteine levels in postmenopausal women with coronary artery disease (CAD) and to investigate associations of homocysteine to other cardiovascular risk factors. Methods: The women in this single-center, controlled, and randomized study were examined at baseline, and after 3 and 12 months, after they had been recruited consecutively from patients referred for investigational coronary angiography. All analyses were performed examiner blind. They were randomized to HRT consisting of transdermal application of continuous 17β-estradiol with cyclic medroxyprogesterone acetate (MPA) tablets for 14 days every 3rd month, or to a control group. Results: After 3 months of unopposed 17β-estradiol, no significant effect on homocysteine was observed compared to the control group. The absolute decrease of 5% in median plasma homocysteine levels after 12-month HRT did not reach statistical significance. Plasma homocysteine seemed slightly higher in women with three- or four-vessel disease, but the difference was not significant. With increasing homocysteine levels, free tissue factor pathway inhibitor (TFPI) antigen increased, whereas E-selectin decreased. In women with diabetes or elevated blood glucose >6.0 mmol/l, plasma homocysteine was correlated to body mass index, C-peptide and insulin as well as age. Conclusion: Transdermal application of 17β-estradiol and sequential MPA do not affect plasma homocysteine in women with established CAD. Plasma homocysteine is stable in women with CAD over time, and unless special intervention is undertaken, repetitive measurements are not necessary in this particular group of high-risk individuals. The circulating anticoagulant TEPI is related to plasma homocysteine.

Aims To assess the adherence to heart failure (HF) guidelines for angiotensin-converting enzyme-I (ACE-I), angiotensin II receptor blockers (ARB), and β-blockers and the possible association of ACE-I or ARB, β-blockers, and statins with survival in the large contemporary Norwegian Heart Failure Registry . Methods and results The study included 5761 outpatients who were diagnosed with HF of any aetiology (mean left ventricular ejection fraction 32% ± 11%) from January 2000 to January 2010 and followed up until death or February 2010. Adherence to treatment according to the guidelines was high. Cox regression analysis to identify risk factors for all-cause mortality, after adjustment for many factors, showed that ACE-I ≥ 50% of target dose, use of beta-blockers, and statins were significantly related to improved survival ( P = 0.003, P < 0.001, and P < 0.001, respectively). Propensity scoring showed the same benefit for these variables. Conclusions Both multivariable and propensity scoring analyses showed survival benefits with β-blockers, statins, and adequate doses of ACE-I in this contemporary HF cohort. This study stresses the importance of guidelines adherence, even in the context of high levels of adherence to guidelines. Moreover, respecting the recommended target doses of ACE-I appears to have a crucial role in survival improvement and, in the multivariate Cox regression analysis, ARB treatment was not significantly associated with a lower all-cause mortality. [10.1093/ehjcvp/pvu015][1] [1]: /lookup/doi/10.1093/ehjcvp/pvu015

Summary Background Sleep-disordered breathing (SDB) is common in heart failure patients. Many of them still remain undiagnosed. The aim of this study was to detect clinical predictors of sleep apnoea which may help to identify patients with SDB at a heart failure clinic. Methods We performed an in-home sleep study on 115 consecutive patients from our heart failure clinic. Clinical characteristics, blood samples, daytime sleepiness and quality of life were registered. Results Among 115 patients, 52% had moderate to severe SDB. Body Mass Index (BMI) ≥ 30 kg/m² was the only independent predictor of moderate to severe SDB [Odds ratio (OR) = 3.62, 95% Confidence interval (CI) 1.40–9.36, p = 0.008]. Quality of life and level of sleepiness were not significantly associated with SDB. Patients with mild to moderate chronic obstructive pulmonary disease (COPD) were unlikely to have SDB compared with patients without COPD (OR = 0.10, 95% CI 0.02–0.43, p = 0.002). Hypertension was a predictor of having obstructive sleep apnoea (OR = 2.78, 95% CI 1.15–6.75, p = 0.02), while haemoglobin ≥ 15 g/dl was associated with central sleep apnoea (OR = 6.71, 95% CI 1.96–22.99, p = 0.002). Conclusion BMI ≥ 30 kg/m2 is associated with moderate to severe SDB, both obstructive and central sleep apnoea. Thus, BMI may be used as one of the selection criteria for referral of heart failure patients to a sleep specialist.

Os I, Hofstad AE, Brekke M, Abdelnoor M, Nesheim BI, Jacobsen AF, Birkeland K, Larsen A, Midtbo K, Westheim A (Ullevaal University Hospital and Aker University Hospital, Oslo, Norway). The EWA (Estrogen in Women with Atherosclerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. J Intern Med 2000; 247: 433–441. Objectives. To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease. Setting. In this single-centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner-blind. Subjects. Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease. Interventions. The women were randomized to HRT, i.e. transdermal application of continuous 17-β oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group. Main outcomes. Effects on lipids and lipoproteins. Results. After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings. Conclusions. In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.

OBJECTIVES The study aimed to assess the hemodynamic and neuroendocrine effects of candoxatril and frusemide compared with placebo in patients with mild chronic heart failure. BACKGROUND Candoxatril is an atriopeptidase inhibitor. It increases circulating levels of atrial natriuretic peptide leading to natriuresis and diuresis, which alleviate the symptoms of a failing heart. METHODS This was a multicenter, randomized, double-blind study. Forty-seven patients with mild stable chronic heart failure received candoxatril 400 mg/day, frusemide 40 mg/day or placebo for up to six weeks. Cardiac indices were determined at rest and during exercise, and blood samples were taken for laboratory analysis. Assessments were performed at baseline (day 0) and after six weeks (day 42). RESULTS In comparison with placebo, both drugs significantly reduced mean pulmonary capillary wedge pressure following the first dose administration. Only candoxatril significantly reduced pulmonary capillary wedge pressure during exercise on day 0, while both drugs significantly reduced this parameter on day 42. Changes in the remaining hemodynamic parameters were comparable for both drugs relative to placebo. Frusemide significantly increased mean plasma renin activity (days 0 and 42), and the mean aldosterone concentration (day 42) in comparison with placebo, whereas candoxatril caused no significant changes in any of the hormonal parameters assessed. CONCLUSIONS These results show that candoxatril, 400 mg/day, has a similar hemodynamic profile to frusemide, 40 mg/day, but it does not induce adverse neuroendocrine effects. Candoxatril therefore appears to offer a clinically significant advantage over frusemide, providing an alternative therapeutic approach to the treatment of patients with mild stable chronic heart failure.

Objectives/Hypothesis Sleep apnea is associated with hypertension and diabetes, putting these patients at high risk for developing cardiovascular disease. The goal of this study was to identify the individual cardiovascular risk profile and to detect premature and undiagnosed disease in patients with various degrees of sleep apnea. Study Design Cross-sectional. Methods Over a 6-month period, we consecutively characterized all patients referred to our sleep laboratory for an initial evaluation of sleep apnea. Clinical history; blood tests with oral glucose tolerance test, when appropriate; test for microalbuminuria; and an electrocardiogram (ECG) were performed. The Framingham general cardiovascular risk score was assessed in each patient. Results A total of 255 patients were evaluated. Of those, 190 (75%) were diagnosed with sleep apnea. Patients with sleep apnea had a significantly higher Framingham risk score than patients without sleep apnea. Adjusted for age and gender, severe sleep apnea was associated with a 60% increased cardiovascular risk compared with not having sleep apnea. In sleep apnea patients without previously diagnosed hypertension, an additional 45% had significant elevated blood pressure. Among sleep apnea patients without known diabetes, we tested 48% with a pathological glucose disposal. Twenty percent of sleep apnea patients without known heart disease had significant ECG changes. Conclusions High Framingham score, undiagnosed hypertension, and pathological glucose disposal were highly prevalent in patients with sleep apnea. Appropriate screening routines are important to detect cardiovascular risk factors in patients with sleep apnea. Level of Evidence 2b. Laryngoscope, 124:306–310, 2014

Background Advances in the understanding of mitral valve pathology have laid to mitral valve plasty (MPL) as the procedure of choice of all the mitral intervention as compared to mitral valve replacement (MVR). This study is aimed to compare the outcome mortality and reoperation and to estimate failure of repair between the two procedures during the follow up time. Material and methods A cohort of 355 patients with mitral valve disease operated between January 1993 to January 2007 with closing date first of mars 2011. There were 214 MPL and 141 MVR at the Hospital discharge. This retrospective cohort had the design of exposed (MPL) versus non-exposed (MVR) with outcome total mortality and reoperation during follow up. Also echocardiography follow-up was undertaken to estimate the true long-term failure rate of repair. Results The mean follow up was 5.3 years SE (3.82) maximum follow up was 14.1 years. Considering the patient time model the association between repair/replacement and total mortality RR = 0.43 95% (0.28-074) p = 0.002 controlling for the confounding effect of 3-vessels disease. Those results were confirmed by propensity score analysis. As far as outcome re-operation, presence of atrial fibrillation AF was an effect modifier indicating lower reoperation rate for MPL compared to MVR for patients without AF, RR = 0.32 95% CL (0.13-0.81) p = 0.017 while no difference in reoperation rates between MPL/MVR for patients with AF RR = 1.82 95% CL (0.52-6.4) p = 0.344. Echocardiography follows up showed incidence of moderate and severe recurrent mitral regurgitation was 1.34 per 100 patients years and 0.27 per 100 patients years during the follow-up time. Conclusion In a cohort of patient with mitral valve disease undergoing MPL/MVR was examined. MPL was associated with better survival, and lower reoperation rate for patients without AF but same rate for patients with AF. We advocate more attention in controlling risk factors of AF in the clinical management of mitral disease. Long-term failure rate of MPL was low during follow up time. A replication of our results by a randomized clinical trial is mandatory.

Chronic heart failure (CHF) is associated with increased inflammation, and exercise training has in some studies been shown to have anti-inflammatory effect, although controversies exist. We investigated the effects of exercise training in CHF patients on markers of inflammation, and further explored any association between inflammation and the severity and etiology of the disease.Eighty patients in stable CHF were randomized to 4 months of group-based high intensity exercise training or to a control group. Physical capacity was measured by 6-minute walk test and cycle ergometer test. Blood samples were drawn at baseline, after 4 months and after 12 months follow-up for analyses of a range of biomarkers.Physical capacity was significantly inversely related to CRP, IL-6, VCAM-1 and TGF-β, and NT pro-BNP levels were significantly correlated to CRP, TNF-α, IL-6, VCAM-1, ICAM-1 and TGF-β (p0.05 for all). Patients with hypertension as etiology of CHF showed higher levels of CRP (p0.01), IL-6 (p = 0.05) and TNF-α (p = 0.02) as compared to other etiologies. No significant differences in changes between the exercise group and the control group were obtained in any of the measured variables, except in patients with idiopathic dilated cardiomyopathy (IDCM), where significant reductions in CRP, ICAM-1, TGF-β and TNF-α levels were observed (p0.05 for all).Measures of CHF severity were significantly correlated with several markers of inflammation. We could not demonstrate over-all anti-inflammatory effect of exercise in this population of CHF patients. However, the etiology of CHF affected the inflammatory profile and the effect of exercise training.

We have previously demonstrated that awareness of high blood pressure may increase blood pressure, plasma catecholamine levels, and stress responses. In the present study, three groups of 19-year-old men, all unaware of their blood pressure status, were selected from the first (group-1, 62 +/- 2 mm Hg, [mean +/- SEM], n = 15), 50th (group-50, 90 +/- 4 mm Hg, n = 15), and 99th (group-99, 123 +/- 5 mm Hg, n = 14) percentiles in causal mean blood pressure at a screening. They were studied (blinded examiners) with intra-arterial blood pressure recordings and multiple measurements of arterial plasma epinephrine and norepinephrine during a mental arithmetic challenge and cold pressor test. Despite high mean blood pressure at the screening, group-99 did not differ from group-50 either in intra-arterial mean blood pressure after 30 minutes of supine rest (89 +/- 3 versus 86 +/- 2 mm Hg) or in serum lipids and resting plasma epinephrine and norepinephrine. However, in group-99 resting plasma epinephrine showed a positive hyperbolic relation to resting diastolic blood pressure (r = .73, P = .004) and a negative hyperbolic relation to the ratio of high-density lipoprotein cholesterol to total cholesterol (r = -.75, P = .002). None of these correlations were present in the two other groups. Furthermore, the three groups differed in heart rate responses (P < .0005) and systolic (P < .0005) and diastolic (P < .05) blood pressure responses to mental arithmetic challenge, group-99 being hyperreactive compared with the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The introduction of beta-blockers in the treatment of cardiovascular diseases was a milestone and one of the most important contributions to clinical medicine in the 20th century. For many years, beta-blockers were considered contraindicated in patients with chronic heart failure owing to the negative inotropic action of these substances. With increasing evidence of neurohormonal activation in heart failure patients, there was a focus on the potential role of beta-blockers in the treatment of chronic heart failure. Several large randomized placebo- controlled clinical trials have shown favorable effects of beta-blockers on mortality and morbidity in heart failure patients with impaired systolic function. Beneficial effects in patients with preserved left ventricular systolic function are less clear. A reduction in heart rate is one of several mechanisms by which beta-blockers exert beneficial effects in chronic heart failure. In this article we present results from major clinical trials examining beta-blocker treatment in chronic heart failure patients and discuss heart rate as a therapeutic target in these patients.

Background Sleep-disordered breathing (SDB) is common in patients with reduced ejection fraction (EF). However, little is known about the prevalence of SDB in a general heart failure population including patients with preserved EF (HFPEF). Methods We prospectively enrolled stable heart failure outpatients from our heart failure clinic to assess the prevalence of SDB independent of systolic left ventricular function. Results Among 115 patients (62% with reduced EF, 38% with preserved EF, New York Heart Association Class II-IV) SDB was present in 81% (27% central sleep apnea, 54% obstructive sleep apnea [OSA]). HFPEF patients had SDB in 80% of the cases, 62% had OSA. This group had significantly more hypertension. Conclusions This study shows a high prevalence of SDB in a general heart failure population, also in patients with HFPEF. These patients have predominantly OSA. Especially in patients with HFPEF SDB should be kept in mind and referral to a sleep specialist should be considered.

Aims To evaluate the quality of life in heart failure (HF) outpatients attending multidisciplinary disease management programmes at HF clinics in Norwegian hospitals. Methods and results Data from HF patients at 24 hospital outpatient clinics were entered in a common database; The Norwegian Heart Failure Registry. Quality of life assessment was done using Minnesota Living with Heart Failure Questionnaire (MLHF). The quality of life assessment was optional at each hospital and was done both at initial evaluation and after 6 months of stable follow-up. A total of 3632 patients were included in the registry and 1778 patients had at least one assessment of quality of life. The mean MLHF score improved significantly from 2.1 at the initial evaluation to 1.4 six months after leaving the clinic (P < 0.001). There was a significant difference in MLHF score between hospitals and baseline MLHF score was significantly associated with NYHA functional class, hospitalizations 6 months before entering the registry, and brain natriuretic peptide; and inversely related to age and systolic blood pressure. Minnesota Living with Heart Failure score was an independent predictor of mortality in this population. Conclusion Quality of life assessed with MLHF improved after follow-up at outpatient HF clinics. Minnesota Living with Heart Failure score was significantly related to functional status, laboratory and demographic variables, and was an important predictor of prognosis.

Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure (CHF). N-terminal pro-B-type natriuretic peptide (NT pro-BNP), is associated with the severity of the disease, and has been reported to be an independent predictor of outcome in CHF. We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF. We have previously reported improved functional capacity in 80 patients after exercise in this exercise program.Seventy-eight patients with stable CHF (21% women; 70+/-8 years; left ventricular ejection fraction 30+/-8.6%) on optimal medical treatment were randomized either to interval training (n=39), or to a control group (n=39). Circulating levels of NT pro-BNP, a six minute walk test (6MWT) and cycle ergometer test were evaluated at baseline, post exercise, and further after 12 months.There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups. Inverse correlations were observed between NT pro-BNP and 6MWT (r=-0.24, p=0.035) and cycle exercise time (r=-0.48, p0.001) at baseline. But no significant correlations were observed between change in NT pro-BNP and change in functional capacity (6MWT; r=0.12, p=0.33, cycle exercise time; r=0.04, p=0.72).No significant changes in NT pro-BNP levels were observed after interval training, despite significant improvement of functional capacity.

Hyperinsulinemia, lipid abnormalities, and impaired fibrinolytic capacity may accompany hypertension, and comprise the metabolic cardiovascular syndrome. They are all independent risk factors for coronary artery disease. Lifestyle modifications can reduce the coronary artery risk. Physical activity has been shown to improve insulin sensitivity, reduce hypertriglyceridemia, improve fibrinolytic capacity, and reduce the blood pressure. A sedentary lifestyle is associated with increased mortality compared to a physically active lifestyle. Hypertensive patients, who often have other atherothrombogenic risk factors, should be encouraged to undertake physical activity as an adjuvant to other nonpharmacological interventions as well as to pharmacological treatment.

The effect of a cold pressor test (CPT) on haemodynamics in relation to general and regional sympathetic activity and arginin vasopressin (AVP), was studied in eleven patients with severe congestive heart failure (CHF). Compared to an age-matched control group (C), resting arterial plasma noradrenaline (NA) (419 +/- 77 vs. 182 +/- 15 pg ml-1), and adrenaline (A) (142 +/- 28 vs 54 +/- 10 pg ml-1) were higher (P less than 0.05) in CHF. AVP showed no significant difference (14 +/- 4 vs. 9 +/- 4 pg ml-1). During CPT systolic and diastolic blood pressure and systemic vascular resistance increased (P less than 0.01), as did NA (delta 114 +/- 39 pg ml-1, P less than 0.01), A (delta 33 +/- 10 pg ml-1, P less than 0.01) and heart rate (delta 10 beats min-1, P less than 0.01). The myocardial v-a difference of NA decreased (P less than 0.05), but was unchanged across the renal vascular bed during CPT. The a-v difference of NA in the hepatic vascular bed, and fractional extraction of A in the coronary sinus, renal and hepatic vascular beds remained unchanged during CPT. AVP did not change significantly and no change in cardiac index or left ventricular filling pressure was observed during CPT. These data suggest that despite an increased activation of the sympathetic nervous system at rest, a further increase in blood pressure and catecholamines took place during CPT. Thus, the effect of a CPT which activates the central sympathetic system seems not to be altered in patients with severe CHF.

Thirty-six, 19-year-old men within the 95th percentile of mean blood pressure (110 mmHg) at a routine medical screening were randomized into two groups and requested to return for a follow-up visit in 2 weeks. One group was sent a neutral letter, while the other was sent a letter conveying the information that their blood pressures were elevated. After 15 min sitting in the laboratory, there was a significantly higher heart rate (P less than 0.05) in the informed group. Thirteen informed and 13 uninformed subjects were examined further by intra-arterial blood pressure recording and serial sampling of arterial catecholamines during cold pressor and mental stress tests. The study was undertaken examiner-blind. Informing the subjects of high blood pressure increased both baseline plasma noradrenaline (P less than 0.01) and adrenaline (P less than 0.05) and intraplatelet noradrenaline (P less than 0.05). Blood pressure (P less than 0.05) and heart rate (P less than 0.05) increased significantly more in the informed group when the subjects were told of the cold pressor test. In addition, there were exaggerated adrenaline (P less than 0.05) and diastolic blood pressure (P less than 0.05) responses to mental stress in the informed group. Thus, awareness of high blood pressure in young men may increase sympathetic tone and responses as measured in the laboratory. Conclusions from studies on early pathogenesis of essential hypertension should therefore be drawn with more caution when patients are aware of their high blood pressure.

The aim of this study was to evaluate the effectiveness of a novel group-based aerobic interval training of high intensity on functional capacity and quality of life in patients with chronic heart failure (CHF) and examine the relation between changes in functional capacity and quality of life. Eighty patients with stable CHF (63 men, 17 women; mean age 70.1 +/- 7.9 [SD] years; left ventricular ejection fraction 30 +/- 8.5%) on optimal medical treatment were randomly assigned to either a 16-week group-based aerobic high-intensity interval training model twice weekly for 65 to 80 minutes/day (n = 40) or a control group (n = 40) that received standard care. Functional capacity was measured using the 6-minute walk test and cycle ergometer test. Quality of life was measured using the Minnesota Living with Heart Failure Questionnaire. After 16 weeks, functional capacity improved significantly in the exercise group compared with the control group measured using the 6-minute walk test (+58 vs -15 meters; p0.001) and for both workload and time measured using the bicycle ergometer test (+10 vs -1 W; p0.001; + 57 vs -8 seconds; p0.001). Quality of life improved significantly in the exercise group compared with the control group (p = 0.03), and a significant inverse correlation was found between quality of life and functional capacity (r = -0.49, p0.05). In conclusion, our exercise model significantly improved functional capacity and quality of life compared with the control group in patients with CHF. Improvements in quality of life were significantly related to functional capacity.

Background and Purpose The purpose of this case report is to describe the responses of 4 patients with chronic heart failure (CHF) to a novel rehabilitation program: a group-based, high-intensity, interval-training program that includes aerobic, resistance, flexibility, and balance activities. Case Descriptions Four patients (55–71 years of age) with CHF (New York Heart Association class III) participated in the rehabilitation program twice per week for 16 weeks. Outcome measures included a 6-minute walk test (6MWT), a cycle ergometer test (aerobic capacity), and a quality-of-life questionnaire. Outcomes Patients 1, 2, and 3 increased their aerobic capacity (17%, 25%, and 52%, respectively). Patient 4 did not complete the cycle ergometer test because of limitations associated with his pacemaker. All patients increased their 6MWT distance (117, 66, 135, and 143 m for patients 1, 2, 3, and 4, respectively). No adverse events were reported. Discussion The Norwegian Ullevaal Model of cardiac rehabilitation is a novel high-intensity, interval-training program. The 4 patients with CHF in this case series who participated in this program experienced improvements in physical capacity and quality of life and had no adverse events. These results are consistent with recent evidence supporting the efficacy of high-intensity interval training in people with CHF. Randomized clinical trials are needed to evaluate the clinical efficacy of this group-based, high-intensity, aerobic interval-training program for patients with CHF.

Nine mild-to-moderate hypertensive patients (HT), aged 41 +/- 0.6 years (mean +/- SEM) and nine age-matched normotensive control subjects (NT) were tilted to 60 degrees for 10 min. During tilt, both systolic (S) blood pressure (BP) (p less than 0.01) and diastolic (D) BP (p less than 0.05) increased in HT, but not in NT. At supine rest renal blood flow was higher in HT than in NT and increased by 17% in HT during tilt, while a decrease of 13% was observed in NT (p less than 0.05). Renal vascular resistance was unchanged in HT during tilt, while a significant increase (p less than 0.01) was observed in NT. Arterial plasma noradrenaline increased in both groups (p less than 0.05) during tilt, significantly more in HT than in NT (p less than 0.05). No statistically significant difference was observed between the groups in renal catecholamine uptake or release. Our data indicate enhanced general sympathetic and circulatory responses to tilt in subjects with mild-to-moderate essential hypertension. However, the enhanced haemodynamic and sympathetic responses were not shared by hypertensive kidneys and renovascular resistance remained unaffected by tilt.

Introduction : Exercise training has been shown to improve exercise tolerance (ET) and quality of life (QoL) in patients with chronic heart failure (CHF). However, the long-term effects of training programs are very spare. We hypothesized that a 4 months group-based aerobic interval-training program would improve ET and QoL in patients with CHF, and after follow-up without supervised exercise training. Methods : Eighty consecutive patients with stable CHF (mean age 70 ± 7.9 years, 63 males), in New York Heart Association-class II-IIIB were randomized to training (n=40) and control (n=40). The ejection fraction was 30.2 % ± 7.6 in the training group and 30.8% ± 9.4 in the control group. All were on optimal medical treatment (93% on beta-blockers and 98% on ACEI inhibitors or A2 receptor blockers at baseline). The training group exercised in a group-based aerobic interval-training model for 50 min, two times a week for 16 weeks. For the next 8 months they only got individual advices to exercise on their own. During the exercise period the patients had 4 consultations with a CHF nurse, including diatory advices, medication adherences, symptom monitoring and social support. In the follow-up period, the patients had 2 consultations with a CHF nurse. The control group received standard medical treatment without additional exercise training. The effects were evaluated by: bicycle ergometer test; 6-minute walk test and Minnesota Living with Heart Failure Questionnaire. Results: After 4 months, both exercise time (+19.2%, p=0.001), workload (+14%, p=0.001) and walking distance (+18%, p Conclusions: Our results support the implementation of a group-based aerobic interval-training program, to improve both ET and QoL in patients with CHF.

The pain experience of patients with heart failure (HF) and its impact on their quality of life (QOL) has not been described in sufficient detail. This study sampled patients hospitalized with HF to describe the prevalence and severity of bodily pain; evaluate differences in bodily pain related to selected demographic and disease-specific characteristics; and evaluate the effect of selected demographic, disease-specific characteristics, bodily pain, and mental health on QOL. Two items from the Medical Outcomes Study--Short Form (SF-36) were used to measure pain, and one subscale of the SF-36 was used to evaluate mental health. The Minnesota Living With Heart Failure Questionnaire was used to measure QOL. Patients with HF (n=93) had a mean age of 75 years, were predominantly male (65%), and lived alone (47.3%). Lung diseases and diabetes were the most common comorbidities; 58% were categorized as New York Heart Association (NYHA) Class III, whereas 58% of the sample was diagnosed with HF in the past four years. Of note, 85% of the patients reported pain and 42.5% said that it was in the severe or very severe range. No demographic variables were associated with pain, whereas a higher number of chronic conditions were associated with pain. SF-36 mental health and pain scores, as well as NYHA class, explained 34.1% of the variance in QOL in patients with HF. These data suggest that pain is highly prevalent and has a significant impact on the QOL of patients with HF. However, additional research is warranted to determine the specific causes and characteristics of pain in these patients.