The Role of Cardiopulmonary Exercise Testing in Hypertrophic Cardiomyopathy.

This review emphasizes the importance of cardiopulmonary exercise testing (CPET) in patients diagnosed with hypertrophic cardiomyopathy (HCM). In contrast to standard exercise testing and stress echoes, which are limited due to the ECG changes and wall motion abnormalities that characterize this condition, CPET allows for the assessment of the complex pathophysiology and severity of the disease, its mechanisms of functional limitation, and its risk stratification. It is useful tool to evaluate the risk for sudden cardiac death and select patients for cardiac resynchronization therapy (CRT), cardiac transplantation, or mechanical circulatory support, especially when symptomatology and functional status are uncertain. It may help in differentiating HCM from other forms of cardiac hypertrophy, such as athletes' heart. Finally, it is used to guide and monitor therapy as well as for exercise prescription. It may be considered every 2 years in clinically stable patients or every year in patients with worsening symptoms. Although performed only in specialized centers, CPET combined with echocardiography (i.e., CPET imaging) and invasive CPET are more informative and provide a better assessment of cardiac functional status, left ventricular outflow tract obstruction, and diastolic dysfunction during exercise in patients with HCM.

Left ventricular remodeling after the first myocardial infarction in association with LGALS-3 neighbouring variants rs2274273 and rs17128183 and its relative mRNA expression: a prospective study.

Post-infarct left ventricular remodeling (LVR) process increases the risk of heart failure (HF). Circulating galectin-3 has been associated with fibrosis, inflammation and cardiac dysfunction during the remodeling process after myocardial infarction (MI). The aims of this prospective case study were to investigate the association of potentially functional variants in the vicinity of LGALS-3 locus, rs2274273 and rs17128183 with maladaptive LVR and whether these variants could affect LGALS-3 mRNA expression in peripheral blood mononuclear cells of patients 6 months after the first MI. This study encompassed 167 patients with acute MI that were followed up for 6 months. Evidence of LVR was obtained by repeated 2D Doppler echocardiography. Rs2274273, rs17128183 and LGALS-3 mRNA expression were detected by TaqMan® technology. Rs2274273 and rs17128183 rare allele bearing genotypes, according to the dominant model (CT+TT vs. CC and AG+GG vs. AA, respectively), were significantly and independently associated with maladaptive LVR (adjusted OR = 3.02, P = 0.016; adjusted OR = 3.14, P = 0.019, respectively) and higher LGALS-3 mRNA expression (fold induction 1.203, P = 0.03 and 1.214, P = 0.03, respectively). Our exploratory results suggest that rs2274273 and rs17128183 variants affect LGALS-3 mRNA and bear the risk for maladaptive LVR post-MI remodeling. Further replication and validation in a larger group of patients is inevitable.

Androgen status in non-diabetic elderly men with heart failure.

PURPOSE: We aimed at evaluating androgen status (serum testosterone [TT] and estimated free testosterone [eFT]) and its determinants in non-diabetic elderly men with heart failure (HF). Additionally, we investigated its associations with body composition and long-term survival. METHODS: Seventy three non-diabetic men with HF and 20 healthy men aged over 55 years were studied. Echocardiography, 6-min walk test, grip strength, body composition measurement by DEXA method were performed. TT, sex hormone binding globulin, NT-proBNP, and adipokines (adiponectin and leptin) were measured. All-cause mortality was evaluated at six years of follow-up. RESULTS: Androgen status (TT, eFT) was similar in elderly men with HF compared to healthy controls (4.79 ± 1.65 vs. 4.45 ± 1.68 ng/ml and 0.409 ± 0.277 vs. 0.350 ± 0.204 nmol/l, respectively). In HF patients, TT was positively associated with NT-proBNP (r= 0.371, p = 0.001) and adiponectin levels (r = 0.349, p = 0.002), while inverse association was noted with fat mass (r = -0.413, p < 0.001). TT and eFT were independently determined by age, total fat mass and adiponectin levels in elderly men with HF (p < 0.05 for all). Androgen status was not predictor for all-cause mortality at six years of follow-up. CONCLUSIONS: In non-diabetic men with HF, androgen status is not altered and is not predictive of long-term outcome.

Renal dysfunction as intrahospital prognostic indicator in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients. METHODS: The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events. RESULTS: Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30-60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243-11.911, p < 0.001; HR 2.554, 95% CI 1.598-4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups. CONCLUSION: Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality.

Predictive value of heart failure with reduced versus preserved ejection fraction for outcome in pulmonary embolism.

AIMS: This study aimed to investigate whether the risk of short-term mortality is different in pulmonary embolism (PE) patients who have heart failure with reduced ejection fraction (HFrEF) as compared with those with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Predictive value of HFrEF or HFpEF for 7-day (intrahospital) and 30-day all-cause mortality was determined in the cohort of 1055 out of 1201 consecutive acute PE patients from the Serbian multicentre PE registry. Patients were classified into either HFrEF or HFpEF group, according to guideline-proposed criteria. A 7-day (intrahospital) and 30-day all-cause mortality was 18.5% vs. 7.3% vs. 4.5% (P < 0.001) and 22.2% vs. 16.3% vs. 7.9% (P < 0.001) for patients with the history of HFrEF, HFpEF, and without HF, respectively. Multivariable analysis adjusted to age, gender, history of chronic obstructive pulmonary disease, diabetes mellitus, arterial hypertension, presence of atrial fibrillation, and mortality risk assessment at admission has shown that only HFrEF, but not HFpEF, was an independent predictor for 7-day mortality (hazard ratio 2.22, 95% confidence interval 1.25-4,38.41, P = 0.021) and neither HFrEF or HFpEF was an independent predictor for 30-day mortality. Among various admission parameters associated to PE outcome, only systolic pressure in HFrEF patients (P < 0.001), heart rate (P = 0.01), and right ventricle systolic pressure (P = 0.039) in HFpEF patients were significantly different in patients who died compared with those who survived at 7 days. CONCLUSIONS: Our study has shown that the presence of previous history of HFrEF, but not HFpEF, in acute PE is an independent risk factor for mortality at 7 days.

Sex-related difference in the prognostic value of syncope for 30-day mortality among hospitalized pulmonary embolism patients.

INTRODUCTION: Recent studies report that syncope is not a significant predictor of 30-day mortality in pulmonary embolism (PE) patients, yet some data suggest sex-related differences may be relevant. OBJECTIVES: To evaluate sex-specific prediction significance of syncope for 30-day mortality in PE patients. METHODS: A multicentric, retrospective, observational, registry-based study on consecutive PE patients was undertaken. Patients were allocated into either a men or a women group before comparisons were made between patients with syncope and those without syncope. A sex-related prediction of the significance of syncope for 30-day mortality was evaluated. RESULTS: Overall 588 patients [294 (50%) men and 294 (50%) women] were included within the study. Among men, patients with syncope were older and had significantly higher parameters of increased 30-day mortality then patients without syncope. Within the same group, however, difference in the 30-day mortality rate was not significant (log rank P = .942). In contrast to the men, fewer differences in admission characteristics were noticed among women, but those with syncope had significantly increased signs of the right ventricular dysfunction and increased 30-day mortality rate, as compared with those without syncope (log rank P = .025). After adjustment for age in a Cox regression analysis, syncope was a significant predictor of 30-day mortality in women (HR = 2.01, 95%CI 1.02-3.95). CONCLUSION: Although syncope is associated with other predictors of higher early mortality in both male and female PE patients, only in women it is a significant predictor of 30-day mortality.

Prognostic value of health-related quality of life in elderly patients hospitalized with heart failure.

Purpose: Previous research has shown that poor health-related quality of life (HRQOL) is associated with adverse long-term prognosis in patients with heart failure (HF); however, there have been inconsistencies among studies and not all of them confirmed the prognostic value of HRQOL. In addition, few studies involved elderly patients and most focused on all-cause mortality and HF-related hospitalization as outcomes. The aim of our study was to determine whether HRQOL is a predictor and an independent predictor of long-term cardiac mortality, all-cause mortality, and HF-related rehospitalization in elderly patients hospitalized with HF. Patients and methods: This prospective observational study included 200 elderly patients hospitalized with HF in Serbia. HRQOL was measured using the Minnesota Living with Heart Failure questionnaire (MLHFQ). The median follow-up period was 28 months. The primary outcome was cardiac mortality, and all-cause mortality and HF-related rehospitalization were secondary outcomes. Survival analysis was conducted using the Kaplan-Meier method and Cox-proportional hazards regression. Results: Subjects with poor HRQOL (higher than the median MLHFQ score) had a higher probability of cardiac mortality (P=0.029) and HF-related rehospitalization (P=0.001) during long-term follow-up. Poor HRQOL was an independent predictor of cardiac mortality (HR: 2.051, 95% CI: 1.260-3.339, P=0.004), all-cause mortality (HR: 1.620, 95% CI: 1.076-2.438, P=0.021), and HF-related rehospitalization (HR: 2.040, 95% CI: 1.290-3.227, P=0.002). Conclusion: HRQOL is an independent predictor of long-term cardiac mortality in elderly patients hospitalized with HF. It also independently predicts all-cause mortality and HF-related rehospitalization. HRQOL could be used as a complementary clinical predictive tool in this patient population.

Biomarkers for the prediction of early pulmonary embolism related mortality in spontaneous and provoked thrombotic disease.

Factors associated with provoked PE may influence a biomarker's predictive value for the primary outcome. The aim of this study was to investigate the value of BNP, cTnI, CRP and D-Dimer measurements taken soon after hospital admission for the prediction of 30-day PE-caused death in patients with spontaneous versus provoked PE.Data were extracted from a pool of 726 consecutive PE patients enrolled in the multicenter Serbian PE registry. Blood concentrations of BNP, cTnI, CRP and D-dimer were measured during the first 24 h of hospitalization. BNP blood level had strong predictive value for the primary outcome in spontaneous PE (c-statistics 0.943, 95% CI 0.882-1.000, p = .001) and a slightly lower predictive outcome in provoked PE (c-statistics 0.824, 95% CI 0.745-0.902, p < .001). NRI and IDI showed that none of the markers, when added to BNP, could improve Cox regression prediction models for 30-day PE-related mortality in either the spontaneous or provoked PE group. Blood levels of BNP measured during the first 24 h of hospital admission had an excellent predictive value for 30-day PE-related mortality in spontaneous PE and slightly lower predictive value in provoked PE, whereas CRP, cTnI and D-Dimer did not contribute significantly to the predictive value of BNP in either group.

CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI.

BACKGROUND: Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event. METHODS: We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis. RESULTS: CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden. CONCLUSIONS: We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications.

Left ventricular diastolic performance at rest is essential for exercise capacity in patients with non-complicated myocardial infarction.

INTRODUCTION: In patients with recent myocardial infarction (MI) limited exercise capacity during physical activity is an important symptom and the base for future treatment. The myocardial injury after MI leads to both systolic and diastolic left ventricular (LV) dysfunction. OBJECTIVE: The aim of this study was to assess the relevance of systolic and diastolic LV function for cardiopulmonary exercise capacity in patients with prior MI. METHODS: Sixty-five consecutive patients after first MI without signs and symptoms of heart failure, aged 52 ± 6 years, were included in the study. The following echo parameters were evaluated: LV ejection fraction (LVEF), peak early and late diastolic velocities (E, A), deceleration time of E wave (dec t E), ratio of early trans-mitral to early annular diastolic velocities (E/e'), velocity propagation of early filling (Vp), and diameters and volumes of LV and left atrium (LA). CPET variables included: oxygen uptake at peak exercise (peak VO2), oxygen pulse (VO2 HR), VE/VCO2 slope, circulatory power (CP) and recovery half time (T1/2). RESULTS: Significant correlations were demonstrated between peak VO2 and E/e' (p < 0.001), peak VO2 and dec t E (p < 0.001), VO2 HR and E/e' (p = 0.002) and between VE/VCO2 and E/e' (p < 0.001). Twenty patients with elevated LV filling pressure achieved significantly lower peak VO2 (1624 vs. 1932 ml, p = 0.027) VO2 HR (11.70 vs. 14.05, p = 0.011) and CP (287,073 vs. 361,719, p = 0.014). By using multivariate regression model we found that only E/e' (p = 0.001) and dec t E (p = 0.008) significantly contributed to peak VO2. CONCLUSIONS: Diastolic dysfunction, particularly LV filling pressure, determine exercise capacity, despite differences in LV ejection fraction in patients with prior MI.

Cardiopulmonary exercise testing and its relation to oxidative stress in patients with hypertension.

An increase in reactive oxygen species has been implicated in the pathologies of hypertension. This study was designed to evaluate antioxidant activity in hypertensive patients and to assess the relationship between oxidative stress and exercise tolerance in hypertensive patients with mild left ventricular diastolic dysfunction (LVDD). A total of 42 patients, aged 51±9 years, with a long history of hypertension and mild LVDD (mitral flow velocities-E/A <1, deceleration time of E >220 ms, and preserved ejection fraction-EF >50%), and 30 controls without cardiovascular disease, aged 50±7 years, underwent cardiopulmonary exercise testing (CPET). Peak oxygen uptake (peak VO(2)), oxygen pulse (VO(2)/heart rate (HR)) and ventilatory anaerobic threshold (VAT) were obtained during CPET. Antioxidant activity of superoxide dismutase (SOD) and glutathione peroxidase in the blood was measured before and after exercise. Reduced peak VO(2) (1715±426 vs. 2083±465 ml min(-1), P<0.001), VO(2)/HR (12.0±2.8 vs. 14.6±3.3 ml per beat, P<0.001) and percentage of peak VO(2) at VAT (55.5±15.8% vs. 64.5±14.7%, P=0.007) were observed in hypertensive patients, compared with controls. Antioxidant protection was significantly attenuated in hypertensive patients, compared with controls, before (945 vs. 1006, P=0.012) and after exercise (954 vs. 1051, P<0.001). The level of SOD before and after exercise was significantly associated with LVDD in hypertensive patients (P=0.012 and 0.02, respectively). In addition, the degree of LVDD before exercise (E/A) influenced the degree of exercise capability (peak VO(2)) (P=0.016). Asymptomatic hypertensive patients with mild LVDD had reduced cardiopulmonary capacity, accurately identified by CPET. The redox state in hypertensive patients was significantly related to LVDD and exercise tolerance. Attenuated antioxidant protection was associated with long-term hypertension.