Heart failure with reduced, mildly reduced, and preserved ejection fraction: outcomes and predictors of prognosis.

INTRODUCTION: Recently, a stratification of the heart failure (HF) phenotypes, which classifies HF into 3 subtypes based on ejection fraction, has been introduced. Before that, clinical trials and registries have been mainly devoted to HF with reduced ejection fraction (HFrEF). As a result, data on long­term survival trends for individual HF phenotypes are scarce. OBJECTIVES: The study aimed to evaluate survival according to the HF phenotype and to identify predictors of mortality. PATIENTS AND METHODS: Patients hospitalized for HF in our referral center between January 2014 and May 2019 were included in the analysis. HF phenotyping was based on EF: reduced (HFrEF with EF <40%), mildly reduced (HFmrEF with EF = 40%-49%), and preserved (HFpEF with EF ≥50%). RESULTS: Of 2601 patients included in the study, 1608 individuals (62%) presented with HFrEF, 331 patients with HFmrEF (13%), and 662 patients with HFpEF (25%). The median follow­up was 2.43 years (interquartile range, 1.56-3.49). The risk of death was 61% higher in HFrEF than in HFpEF (P <0.001), while in HFmrEF and HFpEF it was similar. Survival rates at 1 and 5 years in HFrEF, HFmrEF, and HFpEF were 81%, 84%, 84%, and 47%, 61%, and 59%, respectively. The HF phenotypes differed in most of the parameters that affect prognosis. Only the use of inotropes, which was linked to an increased risk of death, and the use of angiotensin­converting enzyme inhibitors, which reduced this risk, were independent of the HF phenotype. CONCLUSIONS: Survival in HFrEF is worse as compared with HFmrEF and HFpEF, where it is similar. The HF phenotypes differ in most of the parameters that affect survival.

L-arginine and Its Derivatives Correlate with Exercise Capacity in Patients with Advanced Heart Failure.

Methylated arginine metabolites interrupt nitric oxide synthesis, which can result in endothelium dysfunction and inadequate vasodilation. Since little is known about the dynamics of arginine derivatives in patients with heart failure (HF) during physical exercise, we aimed to determine this as well as its impact on the patient outcomes. Fifty-one patients with HF (left ventricle ejection fraction-LVEF ≤ 35%, mean 21.7 ± 5.4%) underwent the cardiopulmonary exercise test (CPET). Plasma concentrations of L-arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured before and directly after CPET. All patients were followed for a mean of 23.5 ± 12.6 months. The combined endpoint was: any death, urgent heart transplantation, or urgent LVAD implantation. L-arginine concentrations increased significantly after CPET (p = 0.02), when ADMA (p = 0.01) and SDMA (p = 0.0005) decreased. The parameters of better exercise capacity were positively correlated with post-CPET concentration of L-arginine and inversely with post-CPET changes in ADMA, SDMA, and baseline and post-CPET SDMA concentrations. Baseline and post-CPET SDMA concentrations increased the risk of endpoint occurrence (HR 1.02, 95% CI 1.009-1.03, p = 0.04 and HR 1.02, 95% CI 1.01-1.03, p = 0.02, respectively). In conclusion, in patients with HF, extensive exercise is accompanied by changes in arginine derivatives that can reflect endothelium function. These observations may contribute to the explanation of the pathophysiology of exercise intolerance in HF.

Epidemiology and clinical characteristics of hospitalized patients with heart failure with reduced, mildly reduced, and preserved ejection fraction.

INTRODUCTION: There is still little information regarding a detailed description and predictors of different subtypes of heart failure (HF) in the Polish population. OBJECTIVES: This study sought to characterize the differences between hospitalized patients with HF divided into HF with preserved ejection fraction (HFpEF; EF ≥50%), mildly reduced EF (HFmrEF; EF 40%-49%), and reduced EF (HFrEF; EF <40%), and to identify factors related to each HF subtype. PATIENTS AND METHODS: Patients from the hospital database whose hospitalization was coded as HF­related between 2014 and 2019 were included in the analysis. RESULTS: A total of 2601 patients were included, of whom 62% had HFrEF, 13% had HFmrEF, and 25% had HFpEF. The patients with HFpEF, as compared with those with HFrEF and HFmrEF, were older (70.5 vs 61.6 vs 66.5 years, P <0.001), less often male (44% vs 68.3% vs 81.3%, P <0.001), and less likely to have an ischemic etiology of HF (19.3% vs 49.8% vs 34.4%, P <0.001) but they were more likely to have hypertension (87.3% vs 78.2% vs 78.2%, P <0.001), atrial fibrillation (64.5% vs 55.6% vs 59.5%, P <0.001), cancer (32.2% vs 19.6% vs 28.7%; P <0.001), and anemia (25.5% vs 15.9% vs 20.5%, P <0.001). Of 3 multivariable models, the one predicting HFpEF was the strongest (P <0.001, area under the curve, 0.79), and included age, sex, aortic stenosis, hypertension, anemia, cancer, thyroid abnormality, atrial fibrillation, longer history of HF, ischemic etiology, coronary artery disease, diabetes mellitus, and liver failure. CONCLUSIONS: HFrEF and HFpEF differed significantly in terms of baseline characteristics, while HFmrEF was in the middle of the HF spectrum, tending to be a mixture of HFpEF and HFrEF characteristics.

Long term outcome of heart failure patients disqualified from heart transplantation.

BACKGROUND: The prognosis of patients with advanced heart failure is unfavourable. However, little is known about the survival of patients referred for heart transplantation but finally disqualified from transplantation due to contraindications. This study aimed to evaluate the prognosis of patients' disqualified from heart transplantation. METHODS: It was a retrospective study based on medical records of patients disqualified from heart transplantation. RESULTS: One hundred and fifty-one patients were included and 94 deaths were recorded during long-term follow-up (range 0.02-10.1 years). The survival rate at 5 years was 25%. The mean age of the studied population was 57.7 years and the majority of patients were males, 87.4%. The ischaemic aetiology (66.2%) was the most dominant aetiology of heart failure. In the Cox regression model, supervision by the specialist cardiology centre (HR 0.61;p = 0.04) and pharmacotherapy with beta-blockers (HR = 0.47;p = 0.02) positively influenced the prognosis. On the contrary, well-known heart failure risk factors like a renal failure (HR 1.59;p = 0.049), pulmonary hypertension (HR 1.55;p = 0.046), liver failure (HR 2.65;p = 0.02) were negative predictors of outcome. By Kaplan-Meier analysis, patients with other than pulmonary hypertension causes of disqualification from heart transplantation had a better survival rate, p = 0.047. CONCLUSIONS: The prognosis of patients disqualified from heart transplantation is unfavourable. However, some of the patients experience relatively long survival. Therefore, careful clinical assessment and identification of factors influencing prognosis may improve adequate patients' qualifications for heart transplantation.

Usefulness of 6-minute walk test, plasma neurohumoral and cytokine activation in the assessment of symptomatic patients with left ventricle dysfunction caused by chronic severe mitral valve regurgitation.

OBJECTIVE: The aim of our study was to select the most relevant markers of impaired left ventricle (LV) function in patients with heart failure (HF) symptoms due to severe chronic mitral regurgitation (MR). METHODS AND RESULTS: Thirty-six patients with decompensated HF due to severe MR underwent echocardiography, 6-minute walk test (6MWT) and measurements of plasma renin activity, angiotensin II, aldosterone, noradrenaline (NA), brain natriuretic peptide (BNP), tumour necrosis factor alpha (TNFalpha) with its receptors, and interleukine-6. Patients presented with significant neurohumoral/cytokine activation. By stepwise multiple regression analysis the strongest prediction model for 6MWT included LVEDVI (R2 = 0.95, P = 0.024), BNP (R2 = 0.67, P = 0.0006), IL-6 (R2 = 0.90, P = 0.044); for BNP: 6MWT (R2 = 0.36, P = 0.003), LA (R2 = 0.56, P = 0.0077), LVESVI (R2 = 0.83, P = 0.0072); for NA: EF (R2 = 0.4 1, P = 0.036), and for TNFalpha: LVESVI (R2 = 0.65, P = 0.003). CONCLUSIONS: 6MWT and neurohumoral markers (mainly BNP, but also NA and TNFalpha) are good predictors of the degree of LV remodelling, showing an independent correlation with the level of LV dilatation/dysfunction in chronic severe MR.These assessments may supplement standard echocardiography in LV decompensation due to severe MR.

[Not only after myocardial infarction - left intraventricular thrombus in the Churg-Strauss syndrome]. / Nie tylko po zawale serca- skrzeplina w lewej komorzew przebiegu zespolu Churga i Strauss.

Churg-Strauss syndrome is a rare systemic disease characterized by necrotising vasculitis and peripheral eosinophilia. Cardiac involvement is found in up to 64% of patients and is given a high rank among the causes of morbidity and mortality. We presented a case of 26 year-old male with Churg-Strauss syndrome and left intraventricular thrombus.

Accurate Noninvasive Assessment of Myocardial Iron Load in Advanced Heart Failure Patients.

BACKGROUND: Heart failure patients presenting with iron deficiency can benefit from systemic iron supplementation; however, there is the potential for iron overload to occur, which can seriously damage the heart. Therefore, myocardial iron (M-Iron) content should be precisely balanced, especially in already failing hearts. Unfortunately, the assessment of M-Iron via repeated heart biopsies or magnetic resonance imaging is unrealistic, and alternative serum markers must be found. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism. METHODS: Left ventricle (LV) myocardial biopsies and serum samples were collected from 33 consecutive HF patients (25 males) with LV dysfunction (LV ejection fraction 22 (11) %; NT-proBNP 5464 (3308) pg/ml) during heart transplantation. Myocardial ferritin (M-FR) and soluble transferrin receptor (M-sTfR1) were assessed by ELISA, and M-Iron was determined by Instrumental Neutron Activation Analysis in LV biopsies. Nonfailing hearts (n = 11) were used as control/reference tissue. Concentrations of serum iron-related proteins (FR and sTfR1) were assessed. RESULTS: LV M-Iron load was reduced in all HF patients and negatively associated with M-FR (r = -0.37, p = 0.05). Of the serum markers, sTfR1/logFR correlated with (r = -0.42; p = 0.04) and predicted (in a step-wise analysis, R 2 = 0.18; p = 0.04) LV M-Iron. LV M-Iron load (µg/g) can be calculated using the following formula: 210.24-22.869 × sTfR1/logFR. CONCLUSIONS: The sTfR1/logFR ratio can be used to predict LV M-Iron levels. Therefore, serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients.

The Association between Serum Levels of 25[OH]D, Body Weight Changes and Body Composition Indices in Patients with Heart Failure.

We try to determine the association between weight changes (WC), both loss or gain, body composition indices (BCI) and serum levels of 25[OH]D during heart failure (HF). WC was determined in 412 patients (14.3% female, aged: 53.6 ± 10.0 years, NYHA class: 2.5 ± 0.8). Body fat, fat percentage and fat-free mass determined by dual energy X-rays absorptiometry (DEXA) and serum levels of 25[OH]D were analyzed. Logistic regression was used to calculate odds ratios for 25[OH]D insufficiency (<30 ng/mL) or deficiency (<20 ng/mL) by quintiles of WC, in comparison to weight-stable subgroup. The serum 25[OH]D was lower in weight loosing than weight stable subgroup. In fully adjusted models the risk of either insufficient or deficient 25[OH]D levels was independent of BCI and HF severity markers. The risk was elevated in higher weight loss subgroups but also in weight gain subgroup. In full adjustment, the odds for 25[OH]D deficiency in the top weight loss and weight gain subgroups were 3.30; 95%CI: 1.37-7.93, p = 0.008 and 2.41; 95%CI: 0.91-6.38, p = 0.08, respectively. The risk of 25[OH]D deficiency/insufficiency was also independently associated with potential UVB exposure, but not with nutritional status and BCI. Metabolic instability in HF was reflected by edema-free WC, but not nutritional status. BCI is independently associated with deficiency/insufficiency of serum 25[OH]D.

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes.

The vast majority of cardiomyopathies have an autosomal dominant inheritance; hence, genetic testing is typically offered to patients with a positive family history. A de novo mutation is a new germline mutation not inherited from either parent. The purpose of our study was to search for de novo mutations in patients with cardiomyopathy and no evidence of the disease in the family. Using next-generation sequencing, we analyzed cardiomyopathy genes in 12 probands. In 8 (66.7%), we found de novo variants in known cardiomyopathy genes (TTN, DSP, SCN5A, TNNC1, TPM1, CRYAB, MYH7). In the remaining probands, the analysis was extended to whole exome sequencing in a trio (proband and parents). We found de novo variants in genes that, so far, were not associated with any disease (TRIB3, SLC2A6), a possible disease-causing biallelic genotype (APOBEC gene family), and a de novo mosaic variant without strong evidence of pathogenicity (UNC45A). The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Moreover, we have identified novel cardiomyopathy candidate genes that are likely to affect immunological function and/or reaction to stress that could be especially relevant in patients with disease onset associated with infection/infestation.

Relationship between renal resistive index and early target organ damage in patients with never-treated essential hypertension.

The aim of our study was to evaluate renal resistive index (RI) value in never treated hypertensive patients in relation to ambulatory blood pressure measurement (ABPM) values and early target organ damage. The study included 318 subjects: 223 patients with never treated essential hypertension (mean age 37.1 years) and 95 normotensive healthy subjects (mean age 37.9 years). ABPM, echocardiography and carotid and renal arteries duplex color Doppler examinations were performed. RI values in patients with never treated essential hypertension were no different from the normotensive control group (0.59 +/- 0.05 vs 0.59 +/- 0.05; NS). In the untreated patients RI correlated significantly with 24-h pulse pressure (r=0.234; p<0.01) and ambulatory arterial stiffness index (AASI) values (r=0.274; p<0.001), intima-media thickness (IMT) (r=0.249; p<0.001), E'/A' (rho= -0.279; p<0.001) and relative wall thickness (RWT; r=0.185; p<0.01). In the multivariate stepwise analysis, RI values correlated independently with carotid IMT (beta=0.272; p=0.020) and 24-h AASI values (beta=0.305; p=0.009). In normotensive healthy controls, significant independent correlation between RI and carotid IMT and 24-h AASI values were also found. Our study may indicate limited value of RI in differentiating patients with uncomplicated hypertension with healthy controls. Renal resistive values were independently correlated with carotid IMT and AASI. These may suggest that renal vascular resistance is related to two markers for cardiovascular events both in the hypertensive and normotensive subjects.

Fluctuations in circulating endothelial progenitor cell levels and acute cardiac graft rejection.

INTRODUCTION: Endothelial progenitor cells (EPCs) in nontransplant settings have reparative properties. However, their role in heart transplantation (HT) is not well defined. OBJECTIVES: The aim of this study was to prospectively evaluate changes in EPC levels in relation to post­HT rejection. PATIENTS AND METHODS: EPC levels were measured in 27 HT recipients for 6 months after HT. Acute cellular rejection (ACR) or antibody­mediated rejection (AMR) were assessed by right ventricular endomyocardial biopsy. RESULTS: ACR and AMR were observed in 7 (25.9%) and 6 (22.2%) patients, respectively. The ACR status at 1 month post­HT did not differ with respect to EPC immediately post­HT. At 1 month post­HT in patients without ACR or AMR, EPC levels were significantly reduced compared with the measurements immediately post­HT (P <0.001). On further follow­up, EPC levels were similar regardless of the rejection events. Nonetheless, greater changes (coefficient of variation) in EPClog (logarithmic transformation) were associated with the risk of AMR or ACR compared with those without any rejection event (median [lower-upper quartile], 15 [13-18] vs 8 [5-13]; P = 0.02 and 22 [14-26] vs 8 [5-13]; P = 0.01, respectively). The receiver operating characteristic curve showed that the coefficient of variation of EPClog of 12 was the optimal cutoff value for the prediction of rejection (area under the curve = 0.85). Higher levels were associated with greater risk of ACR or AMR (P <0.005). CONCLUSIONS: Early reduction of EPC levels was related to a lower risk of ACR or AMR. Greater changes of EPC­levels during follow­up were associated with a significantly higher risk of rejection.

Alterations in calcium regulatory protein expression in patients with preserved left ventricle systolic function and mitral valve stenosis.

BACKGROUND: In heart failure, alterations in the expression of proteins relevant to calcium homeostasis are involved in depressed contractility and diminished relaxation. However the regulation of genes expression is only partially known. The aim was to assess expression of calcium regulatory proteins in left ventricle (LV) myocardium characterised by a preserved global function in mitral valve stenosis (MVS) model but increased neurohumoral/cytokine (N/C) activation. METHODS AND RESULTS: Plasma N/C activation was evaluated in MVS-patients (n = 27), where expression of calcium regulatory proteins (L-type channel, sarcoplasmic reticulum Ca2+-ATPase type2 - SERCA2, Na+/Ca2+ exchanger -NCX, calsequestrin, phospholamban) in LV myocardium was assessed (Western Blot) in comparison with non-failing hearts (NFH). Out of all proteins assessed in MVS, only SERCA2 and NCX expression revealed highly variable changes between subjects, with significant reduction of SERCA2 (15%) level compared to NFH. Moreover, SERCA2 was negatively correlated with BNP (univariate/regression analysis r = -0.63, P = 0.005/r2 = 0.74, P <0.001, respectively), whereas NCX was positively correlated only with noradrenaline (univariate/stepwise analysis r = 0.59 P = 0.002/r2 = 0.59; P = 0.003). CONCLUSIONS: In MVS-patients LV becomes remodelled, although its global function is preserved. It seems that apart from alterations in LV load and wall stress, also such neurohumoral factors as BNP/noradrenaline may influence the Ca2+ handling proteins expression.

Chronic heart failure management in primary healthcare in Poland: Results of a nationwide cross-sectional study.

BACKGROUND: Organizational and educational activities in primary care in Poland have been introduced to improve the chronic heart failure (CHF) management. OBJECTIVES: To assess the use of diagnostic procedures, pharmacotherapy and referrals of CHF in primary care in Poland. METHODS: The cross-sectional survey was conducted in 2013, involving 390 primary care centres randomly selected from a national database. Trained nurses contacted primary care physicians who retrospectively filled out the study questionnaires on the previous year's CHF management in the last five patients who had recently visited their office. The data on diagnostic and treatment procedures were collected. RESULTS: The mean age ± SD of the 2006 patients was 72 ± 11 years, 45% were female, and 56% had left ventricular ejection fraction <50%. The percentage of the CHF patients diagnosed based on echocardiography was 67% and significantly increased during the last decade. Echocardiography was still less frequently performed in older patients (≥80 years) than in the younger ones (respectively 50% versus 72%, Ρ <0.001) and in women than in men (62% versus 71%, P <0.001). The percentage of the patients treated with ß-blocker alone was 88%, but those with a combination of angiotensin inhibition 71%. The decade before, these percentages were 68% and 57%, respectively. Moreover, an age-related gap observed in the use of the above-mentioned therapy has disappeared. CONCLUSION: The use of echocardiography in CHF diagnostics has significantly improved in primary care in Poland but a noticeable inequality in the geriatric patients and women remains. Most CHF patients received drug classes in accordance with guidelines.

Alteration of myocardial sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger expression in human left ventricular volume overload.

BACKGROUND: Reduced myocardial contractility is often attributed to altered Ca(2+) transients and expression of Ca(2+)-ATPase of the SR (SERCA) and Na+/Ca(2+)exchanger (NCX) genes. AIMS: To assess myocardial expression of SERCA and NCX protein levels in left ventricular (LV) remodelling due to chronic severe mitral regurgitation (MR). METHODS: Myocardial expression of SERCA/NCX in biopsy specimens obtained during mitral surgery was assessed in 36 MR patients with LV remodelling and plasma neurohumoral/cytokine activation and in four non-failing hearts (NFH). RESULTS: Myocardial protein levels of SERCA were significantly (20%) lower in the MR group than in NFH group (p=0.016). No significant changes in NCX were observed. However, a lack of homogeneity with regard to SERCA/NCX proteins was observed. Moreover, SERCA was negatively correlated with BNP (r=-0.49, p=0.02), TNFalpha (r=-0.68, p=0.0005) and IL-6 (r=-0.52, p=0.02), whereas NCX was only negatively correlated with TNFalpha (r=-0.62, p=0.002). CONCLUSIONS: MR patients showed wide variations in SERCA/NCX protein expression. Myocardial protein levels of SERCA were significantly lower in the MR population. Moreover, a correlation between BNP, cytokines (IL-6, TNFalpha) and the expression of SERCA/NCX proteins was observed.

Quality of care of hospitalised patients with heart failure in Poland in 2013: results of the second nationwide survey.

BACKGROUND: Optimal management of heart failure (HF) patients is crucial to reduce both mortality and the number of hospital admissions, at the same time improving patients' quality of life. AIM: The aim of the study was to assess the quality of care of hospitalised patients with HF in Poland in 2013 and compare it with the results of a similar survey performed in 2005. METHODS: The presented study was conducted from April to November 2013 in a sample of 260 hospital wards in Poland, recruited by stratified proportional sampling. Similarly to the first study edition in 2005, a trained nurse contacted physicians, who filled out the study questionnaires on the last five patients with HF, who had been discharged from an internal or cardiological ward. HF did not have to be a major cause of hospital admission. RESULTS: The mean age of the 1300 hospitalised patients was 72.1 years, an increase of 2.3 years since the 2005 survey. The proportion of patients classified as New York Heart Association IV decreased from 28.5% in 2005 to 22.1% in 2013. In comparison with 2005, more patients had concomitant disorders such as hypertension (79.5% vs. 71.0%), diabetes (46.2% vs. 33.2%), and chronic renal failure (33.4% vs. 19.4%). Access to echocardiography has improved in recent years: it was available for 98.9% of the surveyed hospital wards (93% in 2005) and it was performed during the hospitalisation in 60.2% of the patients (58.8% in 2005). In 2013 N-terminal pro-B-type natriuretic peptide was accessible for 80.8% of hospital wards (12.8% in 2005) and the test was performed in 31.3% of the hospitalised patients (3.3% in 2005). Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB) were administered in 68.9% of HF discharged patients, beta-blockers in 84.8%, mineralocorticoid receptor antagonist (MRA) in 57.9%, diuretics in 85.9%, and digoxin in 23%. The respective numbers in 2005 were 85.9%, 76.0%, 65.4%, 88.9%, and 38.4%. The decrease in prescription of ACEI or ARB resulted from lesser usage of these drugs in internal medicine wards (from 84.3% in 2005 to 55.6% in 2013). CONCLUSIONS: In comparison to the analogous project run in 2005, an improvement in some areas of HF treatment was observed in Polish hospitals, such as accessibility to echocardiography and natriuretic peptide measurement as well as beta-blocker and MRA use. At the same time, a meaningful decrease in ACEIs or ARBs usage in internal wards was observed, which might be the result of the ageing of the HF population and an increased number of comorbidities.

Role of nondiagnostic exercise-induced ST-segment abnormalities in predicting future coronary events in asymptomatic volunteers.

BACKGROUND: Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. METHODS AND RESULTS: We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression > or =1 mm; 11:2 (n=66), flat or downsloping ST depression > or =0.5 mm and <1 mm; 11:4 (n=124), ST-J depression > or =1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression > or =1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P<0.0001), male sex (RR=1.98, P=0.009), plasma cholesterol (RR=1.02/mg per dL, P<0.0001), hypertension (RR=2.23, P=0.002), duration of exercise (RR=0.71/min, P=0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P=0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P<0.0001), male sex (RR=2.76, P=0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P<0.0001), duration of exercise (RR=0.87/min, P=0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P=0.0005) or 11:5 (RR=2.73, P=0.04) were independent predictors of CE. CONCLUSIONS: Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels > or =1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic.

Home-based telemonitored Nordic walking training is well accepted, safe, effective and has high adherence among heart failure patients, including those with cardiovascular implantable electronic devices: a randomised controlled study.

BACKGROUND: The benefits of rehabilitation in heart failure (HF) patients are well established. Little is known about Nordic walking (NW) training in HF patients especially in those with cardiovascular implantable electronic devices (CIEDs). PURPOSE: The purpose of this study was to assess safety, effectiveness, adherence to and acceptance of home-based telemonitored NW in HF patients, including those with CIEDs (i.e. cardiac resynchronisation therapy, implantable cardioverter-defibrillator). METHODS: The study design was a single-centre, prospective, parallel-group, randomised (2:1), controlled trial among 111 HF patients, New York Heart Association (NYHA) II-III; left ventricular ejection fraction (EF) ≤ 40%. The intervention was a home-based telemonitored eight-week NW (training group (TG) n = 77) five times weekly vs usual care alone (control group (CG) n = 34). Outcome measures included a primary end point of functional capacity assessed by peak oxygen consumption (VO2peak). Secondary end points included: workload duration (t) in cardiopulmonary exercise test (CPET), six-minute walking test (6-MWT) distance and quality of life (QoL), Medical Outcome Survey Short Form 36 (SF-36); safety; adherence to and acceptance of NW. Measurements were made before and after intervention. RESULTS: NW resulted in significant improvement in: VO2peak (16.1 ± 4.0 vs 18.4 ± 4.1(ml/kg/min), p = 0.0001), t (471 ± 141 vs 577 ± 158 (s), p = 0.0001), 6-MWT(428 ± 93 vs 480 ± 87 (m), p = 0.0001) and QoL (79.0 ± 31.3 vs 70.8 ± 30.3 (score), p = 0.0001). We did not observe favourable results in the CG. The differences between the TG and CG were significant in: ΔVO2peak (Δ2.0 ± 2.4 vs Δ-0.2 ± 2.1, p = 0.0004); Δt (Δ108 ± 108 vs Δ0.94 ± 109, p = 0.0031); Δ6-MWT (Δ53.8 ± 63.9 vs Δ22.0 ± 68.7, p = 0.0483). In neither group were there deaths nor necessity for hospitalisation. We did not observe any intervention from CIEDs during NW. All patients in the TG completed rehabilitation and accepted it well. CONCLUSION: In HF patients, including those with CIEDs, home-based telemonitored NW is safe and effective. NW was well accepted by patients and adherence was high and promising.

Prognostic value of novel biomarkers compared with detailed biochemical evaluation in patients with heart failure.

INTRODUCTION: The assessment of prognosis is crucial for the clinical management of patients with heart failure (HF). OBJECTIVES: The aim of the study was to evaluate the usefulness of novel biomarkers for the assessment of prognosis in patients with HF, compared with a detailed assessment based on routine laboratory tests. PATIENTS AND METHODS: The study included 179 patients with HF. In all patients, routine laboratory tests were performed and selected biomarkers were measured (N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, growth hormone, myeloperoxidase, metaloproteinase 9, procollagen type III, soluble toll like receptor 2, insulin growth factor, and neutrophil gelatinase-associated lipocain). The primary endpoint was death or urgent heart transplantation, while the secondary endpoints encompassed primary endpoints plus cardioverter intervention or hospitalization for HF. RESULTS: The mean age of the study group was 52.5 years (91% were men). Most patients had advanced HF. During a 6-month follow-up, 21 primary endpoints and 63 secondary endpoints were recorded. A multiple regression analysis showed that of all laboratory variables and biomarkers, only uric acid and sodium were independent predictors of primary endpoints, and only estimated glomerular filtration rate had a predictive value for secondary endpoints. None of the biomarkers were a significant prognostic factor in the study population. CONCLUSIONS: Biomarkers do not outweigh the value of standard laboratory tests. Routine laboratory workup allows to assess multiorgan damage and provides the most significant prognostic data. Biochemical tests should remain the gold standard for the assessment of prognosis in patients with HF.