Multiparameter diagnostic sensor measurements during clinically stable periods and worsening heart failure in ambulatory patients.

AIMS: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. METHODS AND RESULTS: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment. CONCLUSIONS: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable.

The Impact of Novel Anticoagulants on the Upper Gastrointestinal Tract Mucosa.

Background and objectives: Although treatment with novel oral non-vitamin K antagonist 3anticoagulants (NOACs) is associated with an overall decrease in hemorrhagic complications compared to warfarin, the incidence of gastrointestinal bleeding remains contradictory. Materials and Methods: After the exclusion of patients with pre-existing pathological lesions in the upper gastrointestinal tract (GIT) on esophageal-gastroduodenoscopy (EGD) at entry, a cohort of 80 patients (mean age of 74.8 ± 2.0 years) was randomly divided into four equivalent groups, treated with dabigatran, rivaroxaban, apixaban, or warfarin. Patients were prospectively followed up for three months of treatment, with a focus on anamnestic and endoscopic signs of bleeding. In addition, bleeding risk factors were evaluated. Results: In none of the patients treated with warfarin or NOACs was any serious or clinically significant bleeding recorded within the follow-up period. The incidence of clinical bleeding and endoscopically detected bleeding in the upper GT after three months of treatment was not statistically different among groups (χ2 = 2.8458; p = 0.41608). The presence of Helicobacter pylori (HP) was a risk factor for upper GIT bleeding (p < 0.05), while the use of proton pump inhibitors (PPIs) was a protective factor (p = 0.206; Spearman's correlation coefficient = 0.205). We did not record any post-biopsy continued bleeding. Conclusions: No significant GIT bleeding was found in any of the treatment groups, so we consider it beneficial to perform routine EGD before the initiation of any anticoagulant therapy in patients with an increased risk of upper GIT bleeding. Detection and eradication of HP as well as preventive PPI treatment may mitigate the occurrence of endoscopic bleeding. Endoscopic biopsy during the NOAC treatment is safe.

HeartLogic Multisensor Algorithm Identifies Patients During Periods of Significantly Increased Risk of Heart Failure Events: Results From the MultiSENSE Study.

BACKGROUND: Care of heart failure (HF) patients results in a high burden on healthcare resources, and estimating prognosis is becoming increasingly important to triage resources wisely. Natriuretic peptides are recommended prognosticators in chronic HF. Our objective was to evaluate whether a multisensor HF index and alert algorithm (HeartLogic) replaces or augments current HF risk stratification. METHODS AND RESULTS: MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) enrolled 900 patients with cardiac resynchronization therapy defibrillators enabled for collection of heart sounds, respiration, thoracic impedance, heart rate, and activity data. The HeartLogic algorithm automatically calculated a daily HF index and identified periods IN or OUT of an active alert state relative to a configurable threshold. Patients experienced 192 independently adjudicated HF events (average rate, 0.20/patient-year [pt-yr]) during 1 year of follow-up. HF event rates while IN alert was 10-fold higher than OUT of alert (0.80 versus 0.08 events/pt-yr). Combined with NT-proBNP (N-terminal pro-B-type natriuretic peptide) at enrollment (relative to 1000 pg/mL threshold, event rate was 0.42 [HIGH] versus 0.07 [LOW] events/pt-yr), substratification found the lowest risk group (LOW NT-proBNP and OUT of alert) experienced 0.02 events/pt-yr, whereas the highest risk group (HIGH NT-proBNP and IN alert) was associated with a 50-fold increased risk of an HF event (1.00 events/pt-yr) relative to the lowest risk group. CONCLUSIONS: Dynamic assessment using implantable device sensors within HeartLogic by itself or in conjunction with NT-proBNP measurements can identify time-intervals when patients are at significantly increased risk of worsening HF and potentially better triage resources to this vulnerable patient population. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov. Unique identifier: NCT01128166.

Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial).

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial. Peri-infarct pacing had a neutral effect on long-term remodeling in patients with large first MI. The present analysis includes 109 patients in whom an open artery was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline and 18 months was assessed by transthoracic echocardiography. Multivariable models were fit to identify the independent predictors of LVEDV at baseline and 18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI location (p = 0.03) were independently associated with baseline LVEDV. The following variables were independent predictors of increased LVEDV at 18 months: younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p = 0.03), shorter time from MI to baseline transthoracic echocardiography (p = 0.04), baseline LVEDV (p < 0.0001), and lack of statin use (p = 0.03). In conclusion, patients with large MI and an open infarct artery after PCI, anterior MI location, and male sex were associated with greater baseline LVEDV, but MI location was not associated with 18-month LVEDV. In contrast, younger age, peak creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were associated with long-term LV remodeling.

The prognostic value of high sensitive cardiac troponin I in patients receiving cardiac resynchronisation therapy.

BACKGROUND: Cardiac troponin I (cTnI) is a valuable prognostic biomarker in patients with chronic heart failure (CHF). However, the prognostic importance of cTnI in patients who received cardiac resynchronisation therapy (CRT) remains unknown. The aim of this prospective study was to determine the prognostic value of high-sensitive cTnI (hs-cTnI) in CHF patients receiving CRT. METHODS: We performed measurements of baseline hs-cTnI levels in CRT patients with ischaemic as well as nonischaemic aetiology of CHF, and we investigated their possible association with response to CRT and survival of patients. RESULTS: Ninety consecutive CRT patients (mean age 64 ± 9 years, 71 men) were included. According to the best cut-off value of hs-cTnI level to predict CRT response and all cause mortality, patients were divided into group 1 (hs-cTnI level ≥6.5 ng/l, n = 46) and group 2 (hs-cTnI level <6.5 ng/l, n = 44). During the follow-up period (1155 ± 406 days), 47% of patients were CRT responders (30% in group 1 and 64% in group 2, p = .002) and 31% of patients died from any cause (48% in group 1 and 14% in group 2, p = .001). Regression analysis showed that hs-cTnI level <6.5 ng/l was an independent predictor of CRT response (OR 3.49, p = .019) and that hs-cTnI level ≥6.5 ng/l was an independent predictor of all cause mortality (HR 3.01, p = .021). CONCLUSION: The hs-cTnI can be an useful biomarker with prognostic value in patients receiving CRT.

The effectiveness of CRT on improvement of survival of heart failure patients in real life clinical settings.

Objectives Prolongation of QRS (≥ 120 ms) in patients with heart failure (HF) is associated with higher all-cause mortality than in those with narrow QRS. The aim of our study was to compare the survival of patients with HF and wide QRS after cardiac resynchronization therapy (CRT) with survival of HF patients with narrow QRS and to assess factors predictive of non-response to CRT. Methods We enrolled 680 patients with advanced HF and optimal pharmacologic therapy. All patients were assigned according to duration of QRS complex and implanted device. We acquired two groups. A first group, patients with wide QRS and implanted CRT-D (CRT-D group, n = 354) and a second group, patients having narrow QRS and implanted single/dual chamber ICD (ICD group, n = 326). The primary outcome was death from any cause. The response to CRT was defined as an increase of EF at least by 5% and/or reduction of LVEDD at least by 10%. Results The primary outcome was reached by 84 (23.7%) patients in the CRT-D group and 69 (21.2%) patients in the ICD group. We did not find a statistically significant difference in survival rate between the CRT-D and ICD group [P = 0.44; hazard ratio (HR) 1.132]. Conclusion Survival of patients with HF and wide QRS after CRT implantation is comparable to those with HF and narrow QRS. Coronary artery disease and QRS width less than 145 ms increase risk of non-response to CRT 2.2 and 2.9 times, respectively.

Safety and efficiency of ventricular pacing prevention with an AAI-DDD changeover mode in patients with sinus node disease or atrioventricular block: impact on battery longevity-a sub-study of the ANSWER trial.

AIMS: This ANSWER (EvaluAtioN of the SafeR mode in patients With a dual chambER pacemaker indication) sub-study assesses safety and effectiveness of SafeR™ and the impact of ventricular pacing (VP) prevention on anticipated device longevity and replacement rate. METHODS AND RESULTS: Patients implanted for atrioventricular block (AVB, n = 310) or sinus node dysfunction (SND, n = 336) were randomly assigned to SafeR (n = 314) or DDD (n = 318) and followed for 36 months. Safety, median VP, estimated device longevity (mean difference, 95% confidence interval [CI]), and anticipated replacement rates were analysed by pacing mode and implant indication. No difference in mortality, syncope, or mode intolerance was observed between randomization groups regardless of the indication. Ventricular pacing on SafeR vs. DDD was 11.5 vs. 93.6% in the overall population (P < 0.001), 89.2 vs. 83.8% in permanent AVB (P = 0.944), 53.5 vs. 98.2% in intermittent AVB (P < 0.001), and 2.2 vs. 84.7% in SND (P < 0.001). Anticipated median device longevity increased on SafeR by 14 [Q1 10; Q3 17] months [10; 17] (P < 0.001) in the overall population, 9 months [-5; 22] (P = 0.193) in permanent AVB, 14 months [8; 19] (P < 0.001) in intermittent AVB, and 14 months [9; 19] (P < 0.001) in SND. In intermittent AVB and SND, prolonged estimated battery longevity translated into the prevention of one anticipated replacement in at least 23% of patients. CONCLUSION: SafeR was effective in reducing VP in intermittent AVB and in SND. No effect was observed in permanent AVB. No safety issue was observed. Ventricular pacing reduction by SafeR translated into relevant estimated prolongation of device longevity and anticipated reduction of required replacements.

Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction.

AIMS: We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). METHODS AND RESULTS: A total of 126 patients at 27 international sites within 10 days of onset of anterior or non-anterior MI with creatine phosphokinase >3000 U/L and QRS duration ≤120 ms were randomized 1:1:1 to dual-site biventricular pacing vs. single-site LV only pacing vs. non-implanted control. The primary endpoint was the echocardiographic core laboratory-assessed change in LV end-diastolic volume (ΔLVEDV) from baseline to 18 months between the pooled pacing therapy groups and the control group. ΔLVEDV increased by 15.3 ± 28.6 mL in the control group and by 16.7 ± 30.5 mL in the pooled pacing groups during follow-up (adjusted mean difference (95% CI) = 0.6 (-12.3, 13.5) mL, P = 0.92). There were also no significant between-group differences in the change in LV end-systolic volume or ejection fraction over time. Quality of life, as assessed by the Minnesota Living with Heart Failure (HF) and European Quality of Life-5 Dimension questionnaires and New York Heart Association class, was also similar between groups during 18-month follow-up. Six-minute walk distance improved during follow-up to an equal degree between groups, and there were no significant differences in the 18-month rates of death or HF hospitalization between the pooled pacing therapy vs. control groups (17.4 vs. 21.7% respectively, P = 0.59). CONCLUSIONS: In the present multicentre, randomized trial, peri-infarct pacing did not prevent LV remodelling or improve functional or clinical outcomes during 18-month follow-up in patients with large first MI. CLINICALTRIALSGOV IDENTIFIER: NCT01213251.

A long-term evaluation of cryoballoon ablation in 205 atrial fibrillation patients: a single center experience.

BACKGROUND: Atrial fibrillation is the most prevalent cardiac arrhythmia with significant healthcare impact with regards to treatment costs, morbidity, and mortality. Many of the focal electrical activities that initiate and sustain atrial fibrillation have been found to reside within or near the pulmonary veins. Consequently, pulmonary vein isolation by catheter ablation has emerged as an effective method to eliminate the focal triggers associated with atrial fibrillation. METHODS: In this single-center study, 205 patients were ablated for atrial fibrillation using a cryoballoon catheter and followed-up long-term by retrospective chart examination to evaluate their post-procedural freedom from atrial fibrillation. RESULTS: Patients were followed for up to 6 years with a cohort median of 3 years of post-ablation evaluation. Overall, at 12, 24, and 36 months post-ablation, 71, 49, and 31% of evaluated patients were free of atrial fibrillation, respectively. We found the type of atrial fibrillation (paroxysmal vs. persistent) as an independent predictor for arrhythmia recurrence (HR 1.97; 95% CI: 1.24-3.13, P = 0.006). The cohort median atrial fibrillation-free survival time was 24 months (27 months for paroxysmal atrial fibrillation patients and 14 months for persistent atrial fibrillation patients). There were a total of 37 (18%) complications, 8 (3.9%) were categorized as major complications, all without permanent sequels. The most common complication was phrenic nerve palsy which occurred in 14 (6.8%) patients. CONCLUSION: Long-term outcomes in this study suggest that the pulmonary vein isolation using the cryoballoon technique is relatively an effective method especially in the treatment of paroxysmal atrial fibrillation.

The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial: Design and Rationale.

BACKGROUND: Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. METHODS: The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 µg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. CONCLUSIONS: The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI.

[Importance of EKG in patients wuth resynchronization therapy]. / Význam EKG u pacientov s resynchronizacnou liecbou.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with chronic heart failure. The presence of electrocardiographic (ECG) signs of electrical dyssynchrony during ventricular contractions are an essential criterion for the implantation of CRT. Nevertheless, 1/3 proportion of patients who undergo CRT do not seem to respond favorably. Aim of study was to investigate the relevant ECG parameters prior to CRT (as well as their postimplantation changes) and to determine their relation to predicting favorable response to CRT. METHODS: 52 symptomatic patients (age 62.2 ± 10.5 years, 39 men) with severe left ventricular (LV) systolic dysfunction (ejection fraction 26.3% ± 6.9%) with QRS 120 ms underwent CRT implantation. In early pre- and postimplantation CRT period the following ECG parameters were recorded: QRS complex width and morphology (complete and atypical left bundle branch block, nonspecific intraventricular conduction delay), the size of R and S wave. After 6 months of CRT, responders were definied by improvement of LV ejection fraction > 5 % and/or reduction of end-systolic LV volume > 15 %. RESULTS: The incidence of left bundle branch block (complete or atypical) prior to CRT implantation was higher in responders compared to non-responders group (64% vs 35%, p = 0.036). After implantation of CRT, responders showed significant narrowing of the QRS complex, while non-responder`s QRS complex width remained unchanged (QRS -18 ± 22 ms vs 1 ± 27 ms, p = 0.018). Furthermore QRS complex reduction led to increase in LV ejection fraction (r = 0.47, p = 0.001) and to reduction of LV end-systolic volume (r = 0.42, p = 0.004). R and S changes between responders and non-responders did not differ (p = 0.598 respectively, P = 0.685). CONCLUSION: The presence of complete left bundle branch block before CRT implantation is associated with a better response to CRT compared to other myocardial intraventricular conduction disturbances. Post-implantation narrowing of QRS complex appears to be an early predictor of favorable response to CRT.

Complications of circumferential pulmonary vein isolation using the cryoballoon technique: Incidence and predictors.

BACKGROUND: Cryoballoon ablation technique for the treatment of atrial fibrillation (AF) is a complex procedure consisting of several procedural steps associated with significant risk of complications. The aim of this single-centre study was to give detailed analysis of the complication rate and corresponding risk factors of pulmonary veins cryoisolation (PVI) procedures. METHODS AND RESULTS: A total of 158 consecutive patients (71.5% men, aged 57 ± 9 years, 73.3% paroxysmal atrial fibrillation) were enrolled. Out of 632 pulmonary veins, 96.7% were targeted and isolated by 2-7 applications of cryothermal energy guided with intracardiac echocardiography and fluoroscopy. The additional ablation of cavotricuspid isthmus was performed in 14.6% of procedures. In total, 29 complications were recorded in peri-procedural or early post-procedural period, 8 (5.1%) of them being evaluated as major. No case of permanent injury, disability or death was registered. Multivariate logistic regression showed the persistence of pre-ablation AF as the risk factor of major complications (OR=5.0; ± 95% CI: 1.14-21.97, P=0.033); lower body height was the significant risk factor of any complications (OR=0.95; ± 95% CI: 0.91-0.99, P=0.026) with rapid increase of complication risk with body height ≤ 162 cm. Embolic complications were significantly associated with the pre-ablation AF, while patients with low body height had a trend towards increased risk of phrenic nerve palsy. CONCLUSION: Our study confirmed that the cryoballoon pulmonary vein isolation can be safely performed with low incidence of life-threatening complications which may be further decreased if the mentioned risk factors are handled appropriately.

The occurrence of postoperative atrial fibrillation according to different surgical settings in cardiac surgery patients.

OBJECTIVES: Atrial fibrillation is the most common arrhythmia after cardiac surgery. The pathogenesis of postoperative atrial fibrillation is multifactorial. The aim of the study was to analyse preoperative, intraoperative and postoperative factors and their relationships with the occurrence and duration of atrial fibrillation. METHODS: One hundred and ninety-six patients with coronary heart disease (152 men, age 62.7 ± 10.1 years) underwent surgical revascularization. Extracorporeal circulation was used in 64 patients and minimal extracorporeal circulation was used in 75 patients. Fifty-seven patients underwent surgery without extracorporeal circulation. During the first three postoperative days, subjects were monitored for the duration and incidence of atrial fibrillation, laboratory markers of inflammation (C-reactive protein, leucocytes) and serum potassium. RESULTS: Demographic data and associated cardiovascular diseases in the groups were not statistically different. The overall incidence of atrial fibrillation was 56% (110 patients). The highest incidence of atrial fibrillation was found in the extracorporeal circulation subgroup, with a significantly lower incidence using minimal extracorporeal circulation, and in patients operated on without extracorporeal circulation (75 vs 47 vs 46%, P <0.001). The longest duration of atrial fibrillation was found in patients operated on with extracorporeal circulation compared with minimal extracorporeal circulation, and without extracorporeal circulation (9.7 ± 11.6 vs 4.9 ± 8.3 vs 3.1 ± 5.2, P ≤0.001). The incidence of postoperative atrial fibrillation significantly correlated with elevation of inflammatory markers (C-reactive protein, leucocytes) compared with patients who were free of atrial fibrillation (P ≤0.001, P ≤0.05). The values of serum potassium were not significantly different. The relationship between postoperative atrial fibrillation and echocardiographic parameters was not confirmed. CONCLUSIONS: The use of extracorporeal circulation leads to a higher incidence of postoperative atrial fibrillation compared with the use of minimal extracorporeal circulation or with surgery without extracorporeal circulation, probably due to enhanced systemic inflammatory response.

Oxidative stress in patients with COPD and pulmonary hypertension.

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidant/antioxidant imbalance has also been reported in various forms of pulmonary hypertension. The present study aimed to assess systemic oxidative stress, as reflected by serum malondialdehyde (MDA) concentrations and activities of antioxidant enzymes in erythrocytes [glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in patients with and without pulmonary hypertension secondary to COPD. PATIENTS AND METHODS: Seventy-five patients (58 male) with COPD (mean age 65.1 +/- 1.2 years; mean smoking history 35.6 +/- 3.8 pack-years) were studied. Twenty-one healthy non-smokers served as a control group. Pulmonary function was evaluated with body plethysmography; mean and systolic pulmonary artery pressures (Ppa) were assessed with Doppler echocardiography. Serum concentrations of MDA and activities of GPX, SOD and CAT in washed red blood cells were measured using spectrophotometry. RESULTS: Pulmonary hypertension was present in 28 patients with COPD (systolic Ppa: 46.4 +/- 2.3 mmHg; mean Ppa: 26.0 +/- 1.9 mmHg) and absent in 47 (systolic Ppa: 22.9 +/- 0.8 mmHg; mean Ppa: 13.4 +/- 0.6 mmHg). Compared with the healthy control group, all the patients (with or without pulmonary hypertension) had higher serum MDA concentrations (1.5 +/- 0.1 versus 2.3 +/- 0.1 versus 2.3 +/- 0.1 nmol/mL, ANOVA, P < 0.001) and lower erythrocyte GPX activity (51.3 +/- 3.2 versus 42.2 +/- 2.0 versus 41.3 +/- 2.5 U/g Hb, P = 0.029), whereas SOD (1121.1 +/- 29.0 versus 1032.6 +/- 21.8 versus 1032.7 +/- 36.2 U/g Hb, P = 0.063) and CAT activities (4.9 +/- 0.2 versus 4.6 +/- 0.1 versus 4.7 +/- 0.2 U/g Hb; P= 0.454) were similar. No differences were observed in serum MDA concentrations or activities of GPX, SOD and CAT in erythrocytes between COPD patients with and without pulmonary hypertension. CONCLUSION: The study demonstrates the presence of oxidative/antioxidative imbalance in the systemic circulation in patients with COPD: compared with healthy subjects, COPD patients had higher serum MDA concentrations and lower GPX activity in erythrocytes. The magnitudes of the increase in MDA and reduction in GPX activity were similar in COPD patients with pulmonary hypertension and in those with normal pulmonary artery pressures.

Systemic inflammation in patients with COPD and pulmonary hypertension.

STUDY OBJECTIVES: COPD is a systemic disorder that is associated with increases of inflammatory proteins in systemic circulation. However, no data on the potential role of systemic inflammation in pulmonary hypertension secondary to COPD are available. Therefore, our aim was to investigate the degree of systemic inflammation reflected by circulatory levels of C-reactive protein (CRP), tumor-necrosis factor (TNF)-alpha, and interleukin (IL)-6 in COPD patients with and without pulmonary hypertension. DESIGN: Cross-sectional study. SETTING: University hospital, tertiary referral setting. PATIENTS AND MEASUREMENTS: In 43 consecutive patients with COPD (mean [+/- SD] age, 65.0 +/- 10.5 years; mean FEV(1), 46.2 +/- 18.1% predicted), lung function was assessed using body plethysmography; pulmonary artery pressure (Ppa) levels were measured by echocardiography. Serum TNF-alpha and IL-6 levels were assessed by enzyme-linked immunosorbent assay, and high-sensitivity serum CRP levels were measured by chemiluminescent immunoassay. RESULTS: Pulmonary hypertension was present in 19 patients and was absent in 24 patients. In patients with pulmonary hypertension, serum CRP and TNF-alpha levels were significantly higher than in those patients without hypertension (median, 3.6 mg/L [25th to 75th percentile, 1.4 to 13.0 mg/L] vs 1.8 mg/L [25th to 75th percentile, 0.8 to 2.8 mg/L; p = 0.034]; and median, 4.2 pg/mL [25th to 75th percentile, 3.4 to 10.9 pg/mL] vs 3.1 pg/mL [25th to 75th percentile, 2.1 to 4.2 pg/mL]; p = 0.042, respectively). No differences were seen in serum IL-6 (median, 10.4 pg/mL [25th to 75th percentile, 8.8 to 12.2 pg/mL] vs 10.5 pg/mL [25th to 75th percentile, 9.4 to 39.1 pg/mL]; p = 0.651) between the groups. In multiple linear regression analysis, the following two variables were independent predictors of systolic Ppa (R(2) = 0.373): Pao(2) (p = 0.011); and log-transformed serum CRP level (p = 0.044). CONCLUSION: We conclude that increases in Ppa in patients with COPD are associated with higher serum levels of CRP and TNF-alpha, raising the possibility of a pathogenetic role for low-grade systemic inflammation in the pathogenesis of pulmonary hypertension in COPD patients.

The link between angiotensin-converting enzyme genotype and pulmonary artery pressure in patients with COPD.

OBJECTIVE: The insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of cardiovascular diseases. In patients with primary pulmonary hypertension, the homozygous ACE DD genotype is more prevalent than the non-DD genotype. However, the relationship of ACE gene polymorphism to secondary pulmonary hypertension remains unclear, and ethnicity may be one of the factors that can modulate the effects of ACE genotypes reported in different studies. We hypothesized that in patients with chronic obstructive pulmonary disease (COPD) the presence of the D allele in the ACE gene polymorphism is associated with increased pulmonary artery pressure (Ppa). PATIENTS AND METHODS: Bodyplethysmography was used to assess lung function in 66 consecutive patients with COPD; pulmonary artery pressures were determined using echocardiography. ACE gene I/D polymorphism was identified with the polymerase chain reaction. 118 healthy persons served as the control group. All patients and controls were Caucasian. Genotype II was identified in 15 patients with COPD, genotype ID in 31 and genotype DD in 20. In the control group, genotype II was identified in 19 persons, genotype ID in 68 and genotype DD in 31. The distribution of ACE gene polymorphism did not differ between patients and the control group. RESULTS: In patients with COPD, no differences were seen between the three genotype groups in mean age, smoking history, hemoglobin concentrations or ventilometric or blood gas variables. Both systolic and mean Ppa differed significantly between the II, ID and DD groups (Systolic Ppa: 24.4 +/- 2.2 versus 31.3 +/- 2.5 and 36.7 +/- 3.9 mm Hg, respectively, ANOVA, p < 0.05; Mean Ppa: 13.0 +/- 1.5 versus 17.5 +/- 1.4 and 21.2 +/- 2.8 mm Hg, respectively, ANOVA, p < 0.05). In multiple linear regression analysis, the I/D ACE gene polymorphism (p < 0.05), SaO2 (p < 0.05) and the duration of COPD (p < 0.02) were independent predictors of systolic and mean Ppa. CONCLUSION: The results of the study suggest that I/D ACE gene polymorphism is linked to pulmonary artery pressure in Caucasian patients with COPD.