One-year outcome and durability of pulmonary vein isolation after prospective use of ablation index for catheter ablation in patients with persistent atrial fibrillation.

BACKGROUND: Radiofrequency (RF) catheter ablation for persistent atrial fibrillation (peAF) is associated with less favorable outcomes than for paroxysmal AF (PAF). Recent studies have shown improved clinical outcomes with use of ablation index (AI) targets for pulmonary vein isolation (PVI) in PAF. AI is a novel ablation quality marker that incorporates contact force (CF), time, and power in a weighted formula. This is a single-arm registry to investigate the 1-year efficacy of AF ablation guided by the AI in patients with peAF, and further to evaluate pulmonary vein reconduction at repeat electrophysiology study in case of recurrent AF. METHODS: In total, 55 consecutive patients (69 ± 10 years, 55% male, median time since first AF diagnosis: 31 months (Q1-Q3: 10-70)) with peAF underwent AIguided PVI using a CF surround-flow catheter. AI targets were 600 for anterior and 450 for roof/posterior/inferior antral segments. Patients were monitored for atrial tachyarrhythmia recurrence using 5-day Holter-ECG recordings at 3, 6, and 12 months. RESULTS: The median procedure time was 173 min (Q1-Q3: 152-204). The median fluoroscopy time was 4 min (Q1-Q3: 3-6) and the median fluoroscopy dose was 2.64 Gy/cm2 (Q1-Q3: 1.04-3.99). The median ablation time was 57 min (Q1-Q3: 47-63). At 12 months, 42% of the patients were in sinus rhythm. AF recurrence was seen in 58% of patients. No major complications occurred. CONCLUSIONS: RF ablation using AI in peAF is a feasible and safe technique. At 1 year, AI-guided ablation was associated with AF recurrence in 58% of the patients.

Outcome assessment using estimation of left ventricular filling pressure in asymptomatic patients at risk for heart failure with preserved ejection fraction.

AIMS: High prevalence and lack of pharmacological treatment are making heart failure with preserved ejection fraction (HFpEF) a growing public health problem. No algorithm for the screening of asymptomatic patients with risk for HFpEF exists to date. We assessed whether HFA/ESC 2007 diagnostic criteria for HFpEF are helpful to investigate the cardiovascular outcome in asymptomatic patients. METHODS AND RESULTS: We performed an analysis of the Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST-CHF) that recruited patients with cardiovascular risk factors. All patients underwent a comprehensive diagnostic workup at baseline. Asymptomatic patients with preserved LVEF (>50%) were selected and classified according to HFA/ESC surrogate criteria for left ventricular elevated filling pressure (mean E/e' >15 or E/e' >8 and presence of either NT-proBNP > 220 ng/l, BNP > 200 ng/l or atrial fibrillation) into elevated filling pressure (FPe) or controls. Cardiovascular hospitalizations and all-cause death were assessed for both groups over a 10-year-follow-up.851 asymptomatic patients (age 65.5 ± 7.6 years, 44% female) were included in the analysis. FPe-patients were significantly older (p < 0.001), more often female (p = 0.003) and more often had a history of coronary artery disease, atrial fibrillation and renal dysfunction (p < 0.001, respectively) compared to controls. Incidence of death was significantly higher in the FPe group after a 10-year follow-up (p < 0.001), whereas cardiovascular hospitalization did not differ between groups. CONCLUSION: Asymptomatic patients that fulfill HFA/ESC diagnostic criteria for HFpEF are at higher risk of symptomatic HFpEF and have a worse 10-year-outcome than those who do not fulfill criteria.

Economic impact of heart failure with preserved ejection fraction: insights from the ALDO-DHF trial.

AIMS: Although heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause for hospitalization, its overall costs remain unclear. Therefore, we assessed the health care-related costs of ambulatory HFpEF patients and the effect of spironolactone. METHODS AND RESULTS: The aldosterone receptor blockade in diastolic HF trial is a multicentre, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2011 at 10 sites in Germany and Austria that included 422 ambulatory patients [mean age: 67 years (standard deviation: 8); 52% women]. All subjects suffered from chronic New York Heart Association (NYHA) class II or III HF and preserved left ventricular ejection fraction of 50% or greater. They also showed evidence of diastolic dysfunction. Patients were randomly assigned to receive 25 mg of spironolactone once daily (n = 213) or matching placebo (n = 209) with 12 months of follow-up. We used a single-patient approach to explore the resulting general cost structure and included medication, number of general practitioner and cardiologist visits, and hospitalization in both acute and rehabilitative care facilities. The average annual costs per patient in this cohort came up to €1, 118 (±2,475), and the median costs were €332. We confirmed that the main cost factor was hospitalization and spironolactone did not affect the overall costs. We identified higher HF functional class (NYHA), male patients with low haemoglobin level, with high oxygen uptake (VO2 max) and coronary artery disease, hyperlipidaemia, and atrial fibrillation as independent predictors for higher costs. CONCLUSIONS: In this relatively young, oligosymptomatic, and with regard to the protocol without major comorbidities patient cohort, the overall costs are lower than expected compared with the HFrEF population. Further investigation is needed to investigate the impact of, for example, comorbidities and their effect over a longer period of time. Simultaneously, this analysis suggests that prevention of comorbidities are necessary to reduce costs in the health care system.

Morbidity and mortality in patients with cardiovascular risk factors and obstructive sleep apnoea: results from the DIAST-CHF cohort.

STUDY OBJECTIVES: Aim of the study was to investigate the association between obstructive sleep apnoea (OSA) and cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors. METHODS: In this prospective study, 378 patients of the DIAST-CHF cohort were screened for OSA by home polygraphy. Inclusion criteria were risk factors for diastolic heart failure, such as hypertension, diabetes mellitus, atherosclerotic disease, or history of chronic heart failure. Patients were followed up after 1, 2, 5, 9 and 10 years for the occurrence of major adverse cardiac and cerebrovascular events (MACE and MACCE). RESULTS: 344 patients were included in the analysis, of which 60% were diagnosed with OSA (apnoea-hypopnoea index ≥5/h). Overall mortality was higher in the OSA group (14.9% vs. 5.9%; p = 0.007), but significance disappeared after adjustment for age and sex (hazard ratio (HR) 1.89, 95% confidence interval (CI) 0.86-4.16, p = 0.12). There was no significant difference in the occurrence of MACE or MACCE in patients with OSA compared to those without OSA (MACE: 31% vs. 30%; p = 0.61; MACCE: 32% vs. 30%; p = 0.53). CONCLUSION: We did not find evidence of an adverse effect of OSA on cardiovascular morbidity and mortality in a cohort of patients with cardiovascular risk factors.

B-type natriuretic peptides for the prediction of cardiovascular events and mortality in patients living with HIV: Results from the HIV-HEART study.

AIMS: B-type natriuretic peptide (BNP) has been suggested to improve risk prediction of cardiovascular (CV) events and mortality. We aimed to evaluate the value of BNP to predict the composite primary endpoint of CV events and mortality alongside traditional and HIV specific risk factors in a HIV-infected population. METHODS: In this prospective multicenter HIV-HEART study we followed 808 HIV-positive subjects in the German Ruhr area for a median follow up of 120 (IQR:113-129) months since 2004. Association of BNP with the composite primary endpoint was assessed using Cox regression adjusting for traditional cardiovascular and HIV specific risk factors. RESULTS: At baseline, median BNP was 10.3 (IQR 5.4-18.9) pg/ml. The composite endpoint occurred in 158 (19.6%) patients. Subjects with high BNP levels showed significantly increased frequencies of CV events and death (22% for BNP ≤5 pg/ml, 30% for BNP >5 up to ≤20 pg ml, 38% for BNP >20 up to ≤35 pg ml, 59% for BNP >35 up to ≤100 pg ml and 86% for BNP >100 pg/ml, p-value < 0.01). In the fully adjusted model that included traditional CV risks as well as HIV specific factors, after a log2 transformation, doubling of BNP was significantly associated with increased risk for the composite endpoint (HR:1.16 (95%CI 1.01-1.33); p = 0.031). Comparing BNP of <5 pg/ml to BNP > 100 pg/ml, HR in the fully adjusted model was 3.25 (95%CI 1.50-7.08; p < 0.001). CONCLUSIONS: Increased BNP is associated with significant excess of incident CV events and mortality in HIV-infected patients. BNP is a valuable marker to improve the prediction of CV events and mortality.

Vitamin D deficiency in patients with diastolic dysfunction or heart failure with preserved ejection fraction.

AIMS: Vitamin D deficiency is prevalent in heart failure (HF), but its relevance in early stages of heart failure with preserved ejection fraction (HFpEF) is unknown. We tested the association of 25-hydroxyvitamin D [25(OH)D] serum levels with mortality, hospitalizations, cardiovascular risk factors, and echocardiographic parameters in patients with asymptomatic diastolic dysfunction (DD) or newly diagnosed HFpEF. METHODS AND RESULTS: We measured 25(OH)D serum levels in outpatients with risk factors for DD or history of HF derived from the DIAST-CHF study. Participants were comprehensively phenotyped including physical examination, echocardiography, and 6 min walk test and were followed up to 5 years. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire. We included 787 patients with available 25(OH)D levels. Median 25(OH)D levels were 13.1 ng/mL, mean E/e' medial was 13.2, and mean left ventricular ejection fraction was 59.1%. Only 9% (n = 73) showed a left ventricular ejection fraction <50%. Fifteen per cent (n = 119) of the recruited participants had symptomatic HFpEF. At baseline, participants with 25(OH)D levels in the lowest tertile (≤10.9 ng/L; n = 263) were older, more often symptomatic (oedema and fatigue, all P ≤ 0.002) and had worse cardiac [higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and left atrial volume index, both P ≤ 0.023], renal (lower glomerular filtration rate, P = 0.012), metabolic (higher uric acid levels, P < 0.001), and functional (reduced exercise capacity, 6 min walk distance, and SF-36 physical functioning score, all P < 0.001) parameters. Increased NT-proBNP, uric acid, and left atrial volume index and decreased SF-36 physical functioning scores were independently associated with lower 25(OH)D levels. There was a higher risk for lower 25(OH)D levels in association with HF, DD, and atrial fibrillation (all P ≤ 0.004), which remained significant after adjusting for age. Lower 25(OH)D levels (per 10 ng/mL decrease) tended to be associated with higher 5 year mortality, P = 0.05, hazard ratio (HR) 1.55 [1.00; 2.42]. Furthermore, lower 25(OH)D levels (per 10 ng/mL decrease) were related to an increased rate of cardiovascular hospitalizations, P = 0.023, HR = 1.74 [1.08; 2.80], and remained significant after adjusting for age, P = 0.046, HR = 1.63 [1.01; 2.64], baseline NT-proBNP, P = 0.048, HR = 1.62 [1.01; 2.61], and other selected baseline characteristics and co-morbidities, P = 0.043, HR = 3.60 [1.04; 12.43]. CONCLUSIONS: Lower 25(OH)D levels were associated with reduced functional capacity in patients with DD or HFpEF and were significantly predictive for an increased rate of cardiovascular hospitalizations, also after adjusting for age, NT-proBNP, and selected baseline characteristics and co-morbidities.

Gut Microbiota in Human Immunodeficiency Virus-Infected Individuals Linked to Coronary Heart Disease.

Background: Human immunodeficiency virus (HIV) infection is an independent risk factor for coronary heart disease (CHD) and is associated with perturbation of the gut microbiota. Methods: We analyzed gut microbiota in 30 HIV-infected individuals with CHD (CHD+) and 30 without CHD (CHD-) of the HIV-HEART study group. Results: Gut microbiota linked to CHD was associated with lower α-diversity. Despite insignificant differences in ß-diversity, co-occurrence networks of bacterial genera clearly diverged between CHD+ and CHD- individuals. Multidimensional scaling separated HIV-infected individuals into 2 microbiome clusters, dominated by the genus Prevotella or Bacteroides. The relative abundance of 49 other genera was significantly different between both clusters. The Prevotella-rich cluster was largely composed of men who have sex with men (MSM) (97%), whereas the Bacteroides-rich cluster comprised both MSM (45%) and heterosexual individuals (55%). MSM of the Bacteroides-rich cluster were characterized by reduced α-diversity, advanced immunological HIV stage, longer antiretroviral therapy with more ART regimens, and longer use of protease inhibitors, compared with Prevotella-rich MSM. Conclusions: Community structures of gut microbiota rather than individual species might facilitate risk assessment of CHD in HIV-infected individuals. Sexual behavior appears to be an important factor affecting gut microbiota ß-diversity and should be considered in future studies.

Galectin-3 as a Predictor of Left Ventricular Reverse Remodeling in Recent-Onset Dilated Cardiomyopathy.

OBJECTIVES: Studies have evaluated the association of galectin-3 and outcome in patients with heart failure. However, there is still scarce evidence concerning the clinical usefulness and predictive value of galectin-3 for left ventricular reverse remodeling (LVRR) in patients with recent-onset dilated cardiomyopathy (RODCM). PATIENTS AND METHODS: Baseline galectin-3 was measured in 57 patients with RODCM. All patients were followed for at least 12 months. The study end point was LVRR at 12 months, defined as an absolute improvement of the left ventricular ejection fraction of ≥10% to a final value of ≥35%, accompanied by a decrease in the left ventricular end diastolic diameter of at least 10%, as assessed by echocardiography. In receiver operating characteristic curve analysis, the optimum cut-off value for baseline galectin-3 with the highest Youden index was 59 ng/ml. RESULTS: Overall, LVRR at 12 months was observed in 38 patients (66%). In a univariate analysis, NYHA functional class and baseline galectin-3 levels were associated with LVRR. After adjustment for covariates, galectin-3 remained an independent predictor for LVRR. CONCLUSIONS: Our study suggests that baseline galectin-3 is an independent predictor of LVRR. Low levels of galectin-3 may be regarded a useful biomarker of favorable ventricular remodeling in patients with RODCM.

Clinical predictors of outcome in patients with inflammatory dilated cardiomyopathy.

OBJECTIVES: The study objectives were to identify predictors of outcome in patients with inflammatory dilated cardiomyopathy (DCMi). METHODS: From 2004 to 2008, 55 patients with biopsy-proven DCMi were identified and followed up for 58.2±19.8 months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias. RESULTS: For the primary endpoint, a QTc interval >440msec (HR 2.84; 95% CI 1.03-7.87; p = 0.044), a glomerular filtration rate (GFR) <60ml/min/1.73m2 (HR 3.19; 95% CI 1.35-7.51; p = 0.008) and worsening of NYHA classification during follow-up (HR 2.48; 95% CI 1.01-6.10; p = 0.048) were univariate predictors, whereas left ventricular ejection fraction at baseline, NYHA class at entry, atrial fibrillation, treatment with digitalis or viral genome detection were not significantly related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m2 (HR 3.04; 95% CI 1.21-7.66; p = 0.018) remained a predictor of adverse outcome. CONCLUSIONS: In patients with DCMi, a prolonged QTc interval >440msec, a GFR<60ml/min/1.73m2 and worsening of NYHA classification during follow-up were univariate predictors of adverse prognosis. In contrast, NYHA classification at baseline, left ventricular ejection fraction, atrial fibrillation, treatment with digitalis or viral genome detection were not related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m2 remained independently associated with adverse outcome.

Prolongation of the QTc interval in HIV-infected individuals compared to the general population.

OBJECTIVES: Prolonged QT interval is associated with arrhythmias and sudden death. An increased prevalence of QT interval prolongation in human immunodeficiency virus-infected (HIV) subjects was previously described. The impact of different medications and HIV infection itself on the QT interval is rarely investigated in large HIV+ cohorts. METHODS: We compared QT interval measurement in 496 HIV(+) patients of the HIV-HEART study (HIVH) and 992 sex- and age-matched controls of the population-based German Heinz Nixdorf Recall study (HNR). QT corrected for heart rate (QTc) >440 ms in male and >460 ms in female was considered pathological. We analysed the impact of HIV status and HIV medication on QTc prolongation in the HIVH subjects. RESULTS: We observed longer QTc in HIVH subjects compared with HNR controls: 424.1 ms ± 23.3 vs. 411.3 ± 15.3 ms for male and 435.5 ms ± 19.6 vs. 416.4 ms ± 17.3 for female subjects (p < 0.0001 for both sexes). Adjusting for QT prolonging medication the mean differences in QTc between the two studies remained significant with 12.6 ms (95% CI 10.5-14.8; p value <0.0001) for male and 19.3 ms (95% CI 14.5-24.2; p value <0.0001) for female subjects. Prolongation of QTc was pathologic in 22.8 vs. 3.9% of HIV(+) and non-infected males and in 12.1 vs. 1.8% of the females [OR of 7.9 (5.0-12.6) and OR of 6.7 (1.8-24.2), respectively]. Smoking behaviour was an independent factor to lengthen QTc in HIV(+) patients. Diabetes mellitus was not a risk factor itself, but might be associated with medication which was associated with LQT. We could not observe any influence of the HIV status, ART, or any co-medication on the QTc. CONCLUSIONS: Our study showed that HIV(+) patients had significantly longer QTc intervals compared to the general population. The number of patients with pathologic QTc prolongation was significantly increased in HIV(+) population.

Ghrelin and hormonal markers under exercise training in patients with heart failure with preserved ejection fraction: results from the Ex-DHF pilot study.

BACKGROUND: Over 50% of patients with symptomatic heart failure (HF) experience HF with preserved ejection fraction (HFpEF). Exercise training (ET) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF. A systemic pro-inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF. ET modifies myocardial structure and has been related to inflammatory state. We investigated Ghrelin, related adipokines, markers of inflammation, and neuro-hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF. METHODS AND RESULTS: Ex-DHF-P was a prospective, controlled, randomized multi-centre trial on structured and supervised ET in patients with HFpEF. We performed a post hoc analysis in 62 patients from Ex-DHF-P. Ghrelin, adiponectin, leptin, IL-1ß, IL-6, IL-10, tumour necrosis factor-alpha, MR-proANP, MR-proADM, CT-proET1, and CT-proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF. Thirty-six (58%) patients were female, mean age was 64 years, and median ghrelin was 928 pg/mL (interquartile range 755-1156). When stratified for high versus low ghrelin, groups significantly differed at baseline in presence obesity, waist circumference, and adiponectin levels (P < 0.05, respectively). Overall, ghrelin levels rose significantly to 1013 pg/mL (interquartile range 813-1182) (P < 0.001). Analysis of covariance modelling for change in ghrelin identified ET (P = 0.013) and higher baseline adiponectin levels (P = 0.035) as influencing factors. CONCLUSIONS: Exercise training tended to increase ghrelin levels in Ex-DHF-P. This increase was especially pronounced in patients with higher baseline adiponectin levels. Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinically meaningful surrogate parameters.

Long-term outcome and predictors of outcome in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: The study objectives were to identify predictors of outcome and to assess the long-term outcome in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: From 2004 to 2008, 206 consecutive patients (age 52.1±12.6years) with non-ischemic DCM were prospectively enrolled in the study and followed up for a mean of 55.6±18.4months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of all-cause mortality or heart transplantation. During the follow-up period 47 patients died (22.8%) and 5 patients (2.4%) underwent heart transplantation for end-stage heart failure. For the primary end point, a systolic LVEF <35% (hazard ratio 2.56; 95% confidence interval 1.21-5.45; p=0.014), a prolonged QTc interval >440ms (hazard ratio 2.56; 95% confidence interval 1.24-3.83; p=0.007) and a GFR <60ml/min/1.73m(2) (hazard ratio 2.42; 95% confidence interval 1.36-4.29; p=0.003) were identified as independent predictors, whereas the presence of an LBBB, atrial fibrillation, mild mitral regurgitation or treatment with digitalis were not significantly related to outcome. CONCLUSIONS: In patients with non-ischemic DCM, a reduced systolic LVEF <35%, a prolonged QTc interval >440ms and an abnormal renal function with a GFR <60ml/min/1.73m(2) are independent predictors of death or need for heart transplantation.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Feasibility of VECOPA, a dose-intensive chemotherapy regimen for children and adolescents with intermediate and advanced stage Hodgkin lymphoma: results of the GPOH-HD-2002/VECOPA pilot trial.

The GPOH-HD (Gesellschaft für Pädiatrische Onkologie und Hämatologie-Hodgkin Disease) strategy for children and adolescents with intermediate and advanced stage Hodgkin lymphoma is based on two induction cycles of OEPA (vincristine, etoposide, prednisone, doxorubicin) followed by COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or COPDAC (cyclophosphamide, vincristine, prednisone, dacarbazine) consolidation. The feasibility and efficacy of an intensified procarbazine-free consolidation regimen VECOPA (vinblastine, etoposide, cyclophosphamide, vincristine, prednisone, doxorubicin) were investigated. Following two OEPA and one or two VECOPA cycles, involved field radiotherapy was applied. The main endpoint was feasibility. Secondary endpoints were toxicity, proportion of delayed cycles, granulocyte-colony stimulating factor use, and event-free and overall survival. The regimen was well tolerated with mostly hematotoxicity exceeding Common Toxicity Criteria grade 2. In most patients with advanced stage the second VECOPA cycle was delayed despite hematopoietic recovery and absence of serious adverse events. Event-free survival at 36 months was 0.86 (95% confidence interval 0.70-1). The VECOPA regimen is effective and tolerable. However, its time-intensification was not fully exploited within this trial.

Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial.

AIMS: Galectin-3 is a marker of myocardial fibrosis and mediates aldosterone-induced cardiovascular inflammation and fibrosis. Characteristics of galectin-3 and its response to spironolactone have not been evaluated in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to determine the association between galectin-3 levels and patient characteristics in HFpEF; to evaluate the interaction between spironolactone and galectin-3 levels; and to assess the association between galectin-3 and clinical outcomes. METHODS AND RESULTS: Aldo-DHF investigated spironolactone 25 mg once daily vs. placebo for 12 months in patients with NYHA class II-III, LVEF ≥50%, grade ≥ I diastolic dysfunction, and peakVO2 ≤ 25 mL/kg/min. Galectin-3 levels were obtained at baseline, and at 6 and 12 months. The association between baseline galectin-3, change in galectin-3, and all-cause death or hospitalization was evaluated, and the interaction between galectin-3 and treatment was assessed. Median baseline galectin-3 was 12.1 ng/mL. After multivariable adjustment, baseline galectin-3 inversely correlated with peak VO2 (P = 0.021), 6 min walk distance (P = 0.002), and Short Form 36 (SF-36) physical functioning (P = 0.001), and directly correlated with NYHA class (P = 0.007). Baseline NT-proBNP correlated with E/e' velocity ratio (P ≤ 0.001), left atrial volume index (P < 0.001), and LV mass index (P = 0.009). Increasing galectin-3 at 6 or 12 months was associated with all-cause death or hospitalization independent of treatment arm [hazard ratio (HR) 3.319, 95% confidence interval (CI) 1.214-9.07, P = 0.019] and NT-proBNP (HR 3.127, 95% CI 1.144-8.549, P = 0.026). Spironolactone did not influence galectin-3 levels. CONCLUSION: Galectin-3 levels are modestly elevated in patients with stable HFpEF and relate to functional performance and quality of life. Increasing galectin-3 was associated with worse outcome, independent of treatment or NT-proBNP.

Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up.

INTRODUCTION: Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. METHODS: The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. RESULTS: 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88-0.94]) and ART (per y: HR: 0.81 [0.79-0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8-482.8) versus 574 cells/µL (IQR: 406-786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies/mL and median CD4-cells 542.5 cells/µL (IQR: 370-793.5). CONCLUSIONS: Advanced clinical and immunological stages of HIV-infection, but not the duration of ART, were associated with higher incidences of CVE and deaths in the HIVH cohort. These observations support an earlier initiation of ART in HIV+. Special cardiovascular risk calculations for HIV+ should consider immunological and clinical categories of the HIV-infection.

Impact of obstructive sleep apnoea on diastolic function.

We investigated whether obstructive sleep apnoea (OSA) independently affects diastolic function in a primary care cohort of patients with cardiovascular risk factors. 378 study participants with risk factors for diastolic dysfunction were prospectively included and a polygraphy was performed in all patients. Diastolic dysfunction was assessed by comprehensive echocardiography including tissue Doppler. Sleep apnoea was classified according to apnoea/hypopnoea index (AHI) as none (AHI <5 events·h(-1)), mild (AHI ≤5 to <15 events·h(-1)) or moderate-to-severe (AHI ≥15 events·h(-1)). Patients with central sleep apnoea (n=14) and patients with previously diagnosed sleep apnoea (n=12) were excluded. In the remaining 352 subjects, 21.6% had an AHI ≥15 events·h(-1). The prevalence of diastolic dysfunction increased with the severity of sleep apnoea from 44.8% (none) to 56.8% (mild) to 69.7% (moderate-to-severe sleep apnoea) (p=0.002). The degree of diastolic dysfunction also increased with sleep apnoea severity (p=0.004). In univariate regression analysis, age, desaturation index, AHI, cardiac frequency, angiotensin receptor 1 antagonist therapy, body mass index (BMI) and left ventricular mass were associated with diastolic dysfunction. In multivariate regression analysis, only age, BMI, AHI and cardiac frequency were independently associated with diastolic dysfunction. Moderate-to-severe OSA is independently associated with diastolic dysfunction in patients with classical risk factors for diastolic dysfunction.