Chronic Heart Failure NYHA Class Research Articles

The value of percutaneous transcatheter mitral valve regurgitation repair in the combination treatment of chronic heart failure patients: Results from a 6-month observational prospective study

Rationale: Surgical interventions have been recognized as the main method to repair of valvular disorders. Percutaneous transcatheter intervention with a clipping system is being actively introduced into the treatment of chronic heart failure (CHF) patients and mitral valve insufficiency (MVI) for correction of mitral regurgitation (MR), along with drug therapy. Aim: To establish the effect of the mitral valve leaflet clipping in the combination treatment of CHF patients on the clinical course of heart failure and the remodeling process. Methods: This single center prospective comparative study included 80 patients with CHF NYHA class II–IV and secondary MR grade 3–4. The patients were on optimal medical treatment (OMT) for CHF for at least 3 months before inclusion into the study. The main group included 55 patients who underwent transcatheter mitral valve repair with the use of MitraClip system, and the control group consisted of 25 patients in whom the surgery for MR was waived for various reasons (refusal of the surgery by the patient, some valve characteristics), and only OMT for CHF was used. At baseline, main clinical and demographic characteristics of the patients in the both groups were comparable. The duration of the follow-up was 6 months. Echocardiography (echoCG), a 6-minute walk test, and measurements of the brain natriuretic propeptide level were performed in all patients at baseline and at 6 months of the follow-up. Results: At 6 months, there was a significant reduction in CHF NYHA class and an increase in the 6-minute walk test distance and a decrease in diuretic requirements (converted to furosemide, from 58.4 ± 17.2 to 38.1 ± 20.7 mg daily, р = 0.02) in the group with the MitraClip implant, but not in the control group. In the OMT only group, there were no changes over 6 months in the diuretic requirements (48.1 ± 6.68 and 43.8 ± 27.15 mg daily, respectively, р = 0.8). The number of hospital readmissions due to CHF decompensation was 7 (12.7%) in the implanted MitraClip group and 4 (16%) in the OMT group (р = 0.69). EchoCG performed at 6 months after the surgical intervention identified no cases of MR grade 2. In the MitraClip implant group, there was a decrease in the size and volumes of the left atrium (р = 0.02 and р = 0.05, respectively), left ventricle (for end-diastolic diameter p = 0.002, end-diastolic volume p = 0.03), mean pulmonary artery pressure (p = 0.03), as well as an increase in cardiac output (р = 0.04). In the patients receiving OMT only, there were no significant changes in EchoCG parameters over time. Conclusion: Our study has shown benefits of the implantation of the mitral valve leaflet clipping system, compared to OMT only, in CHF. The clipping procedure promotes a significant improvement in clinical course of CHF, reverse myocardial remodeling, and reduction in diuretic requirements.

ДОЛГОСРОЧНАЯ ЭФФЕКТИВНОСТЬ УСИЛЕННОЙ НАРУЖНОЙ КОНТРПУЛЬСАЦИИ У ПАЦИЕНТОВ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ ИШЕМИЧЕСКОГО ГЕНЕЗА

Aim. To study the long-term effect of complex therapy with the addition of enhanced external counterpulsation (EECP) on exercise tolerance, quality of life and systolic heart function in patients with ischemic chronic heart failure (CHF). Material and methods. Patients with ischemic CHF NYHA class II-III (n=20) included in the study. Patients, in addition to optimal medical therapy, were treated with EECP (35 hours, the standard protocol, 1 course every 6 months). The duration of observation was 5 years. Baseline, 12, 24, 36, 48 and 60 months performed assessment of NT-proBNP level, clinical status, exercise tolerance (6-minute walk test – 6MWT), quality of life (Minnesota Living with Heart Failure Questionnaire – MLHFQ), left ventricular ejection fraction (LVEF) according to echocardiography. The composite primary endpoint (CPE) included adverse cardiovascular events, new cases of atrial fibrillation (AF), diabetes mellitus (DM), decreased renal function, and hospitalizations due to CHF. Results. During the observation period (60 months), significant stable positive dynamics were noted in exercise tolerance (6MWT distance increased by 59.3%), clinical status, LVEF, NT-proBNP level, quality of life (MLHFQ). The incidence of myocardial infarction was 5%, revascularization – 15%, new cases of AF – 5%, decreased renal function – 10%, hospitalizations for CHF – 35%. There were no cases of strokes, deaths or new cases of diabetes. The prevalence of CPE was 70% over a 5-year period. Conclusion. A stable positive effect of EECP treatment of patients with ischemic heart failure on functional status and clinical outcomes has been demonstrated.

ДОЛГОСРОЧНЫЕ СОСУДИСТЫЕ ЭФФЕКТЫ УСИЛЕННОЙ НАРУЖНОЙ КОНТРПУЛЬСАЦИИ У ПАЦИЕНТОВ С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА, ОСЛОЖНЕННОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ

Aim. To study the long-term effect of complex therapy with the addition of enhanced external counterpulsation (EECP) on the structural and functional parameters of the cardiovascular system in patients with ischemic chronic heart failure (CHF). Material and methods. Patients with ischemic CHF NYHA class II-III (n=59; median age 64.8 [57.6; 71.2] years; 81.4% men), receiving EECP in addition to optimal medical treatment (35-hour course every 6 months; compression pressure 220-280 mmHg) had an assessment of exercise tolerance (distance in the 6-minute walk test; 6MWT), structural and functional state of large vessels and microvasculature (computer video capillaroscopy of the periungual bed, photoplethysmography, applanation tonometry), assessment of echocardiographic parameters (volume dimensions, systolic and diastolic functions of the left ventricle) at baseline, after 12, 24 and 36 months. The follow-up period was 36 months. Results. Significant stable positive dynamics of tolerance to physical activity (the distance in the 6MHT increased by 59.4%) was found. Functional parameters of the heart (LVEF from 40.6 [34.6; 43.2] to 49.2 [43.0; 52.7] %, p=0.003; NT-proBNP from 246 [167; 341] to 120 [93; 148] pg/ml), large (occlusion index by phase shift) and small (occlusion index by amplitude, percentage of perfused capillaries, percentage of capillary restoration) vessels significantly improved already in the first year of observation, while structural parameters (volume dimensions; indexed LV myocardial mass from 94.3 [79.4; 97.4] to 121 [109; 134] g/m2, p=0.010; radial augmentation index, stiffness index, occlusion index) began to change significantly by 2-3-years. Conclusion. A stable positive effect of EECP treatment in patients with ischemic heart failure on the structural and functional parameters of the heart and blood vessels has been demonstrated. At the same time, the rate of improvement in functional indicators was much faster than that of structural parameters.

Acute Kidney Injury after Transcatheter Aortic Valve Implantation

Aim. The aim of the study was to evaluate the incidence and predictors of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI).Material and methods. 50 patients (39 women, 11 men) aged 76 (71; 80) years who underwent TAVI were examined. One day after TAVI, blood creatinine level was determined by the Jaffe method and troponin I by a highly sensitive method (hs-cTnI). Acute kidney injury (AKI) was diagnosed according to the KDIGO criteria (2012). The following hospital complications were evaluated: cases of cardiac death, intraoperative myocardial infarction (MI), stroke and transient ischemic attack, permanent pacemaker implantation, recurrent paroxysms of atrial fibrillation.Results. History of MI had 22% of patients, percutaneous coronary intervention – 38%, hypertension – 98%, chronic kidney disease – 48%, diabetes mellitus – 24%, class II NYHA of chronic heart failure (CHF) – 52%, NYHA class III – 46%, NYHA class IV – 2%. The risk of operational mortality according to EuroSCORE II was 6.3±5.4%. AKI after TAVI was registered in 6 (12%) patients (1 grade AKI – 8%, 2 grade – 2%, 3 grade – 2%). Parameters associated with AKI after TAVI were higher CHF NYHA class (p=0,020), high hs-cTnI level (p=0,013), intraoperative MI (p=0.035). The predictor of AKI after TAVI was high hs-cTnI level (odds ratio 4.0, 95% confidence interval 1.0-16.1). Among patients with AKI after TAVI in compare with patients without AKI, the cumulative frequency of cardiac death, MI, strokes and transient ischemic attacks, implantation of a permanent pacemaker, the proportion of people with paroxysmal atrial fibrillation during the hospital stay was 5,8 times higher (66.7% vs 11.4% respectively, p=0.001).Conclusion. AKI after TAVI was present in 12% of patients. The predictor for AKI development was an increase in hs-cTnI level after TAVI implantation. The hospital prognosis after TAVI is worse in patients with postoperative AKI.

Mortality risk factors in patients who are in heart transplantation waiting list

Objective: to estimate the survival of patients in the heart transplantation waiting list (HTx WL) at Almazov National Medical Research Centre (V.A. Almazov NMRC), Saint-Petersburg, Russia, from 2010 to 2018 and to define factors for death among these patients.Materials and methods: it was a single-centre retrospective study involving 151 patients with end-stage chronic heart failure (CHF) classes III-IV (NYHA) in the HTx WL.Results: the dynamic of decreasing mortality was revealed. Based on the results of constructing the discriminant function, four factors predicting the survival of patients in the HTx WL, namely, ACE inhibitors/ARBs, beta-blockers, status 1 of UNOS, CHF NYHA class IV, were pointed out. The model has sufficient resolving power but is not capable of predicting the outcome in the presence of acute decompensation of CHF.Conclusion: mortality in the HTx WL for the period 2010-2018 decreased that was associated with an active implementation of cardiac surgical methods as a «bridge» to transplant and optimal medical therapy, including ACE inhibitors/ARBs and beta-blockers in patients supported with inotropes (UNOS 1B). The greatest risk of mortality was found in CHF class IV and status 1 by UNOS.

Long-term results of cardiac contractility modulation in patients with chronic heart failure

Aim. Evaluate the overall effectiveness of cardiac contractility modulation (CCM) therapy in patients with chronic heart failure of various etiology.Methods. The study included 61 patients with chronic heart failure (NYHA class II-III), ejection fraction 20-40% and narrow QRS <130 ms, who were implanted the CCM devices. Depending on the etiology of heart failure, ischemic cardiomyopathy prevailed (41 patients). All patients were performed echocardiography, 6-min walk test and Minnesota Living with Heart Failure questionnaire (MHFLQ). Results. The observation period was 25 months. All 54 patients significantly improved left ventricular ejection fraction from 32.2% to 37.6% (р=0.026) and volume parameters (left ventricle end systolic volume from 150 to 137 ml (р=0.034), left ventricle end diastolic volume from 220 to 201 ml (р=0.044), reduced the heart failure NYHA class >1 in 29 (53.7%) patients (р=0.015), increased 6-min walk test from 265 to 343 m (р=0.029), and the MHFLQ improved from 46.1 to 35.8 (р=0.042). Non-ischemic cardiomyopathy was associated with significant improvement in MHFLQ (from 42.7 to 30.3, р=0.029) and lowering the heart failure NYHA class>1 (83.3%, vs 47.2%, p=0.012) compared to ischemic group. Conclusion. CCM is safe and effective in patients with chronic heart failure NYHA class II-III, ejection fraction 20- 40% and narrow QRS˂130 ms, who were implanted the CCM devices. Depending on the etiology of heart failure, ischemic cardiomyopathy prevailed (41 patients). All patients were performed echocardiography, 6-min walk test and Minnesota Living with Heart Failure questionnaire (MHFLQ).Results. The observation period was 25 months. All 54 patients significantly improved left ventricular ejection fraction from 32.2% to 37.6% (р=0.026) and volume parameters (left ventricle end systolic volume from 150 to 137 ml (р=0.034), left ventricle end diastolic volume from 220 to 201 ml (р=0.044), reduced the heart failure NYHA class >1 in 29 (53.7%) patients (р=0.015), increased 6-min walk test from 265 to 343 m (р=0.029), and the MHFLQ improved from 46.1 to 35.8 (р=0.042). Non-ischemic cardiomyopathy was associated with significant improvement in MHFLQ (from 42.7 to 30.3, р=0.029) and lowering the heart failure NYHA class>1 (83.3%, vs 47.2%, p=0.012) compared to ischemic group.Conclusion. CCM is safe and effective in patients with chronic heart failure NYHA class II-III, ejection fraction 20- 40% and narrow QRS˂130 ms. Non-ischemic etiology of cardiomyopathy was associated with significant improvement in MHFLQ and lowering the heart failure class.

Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study.

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies. In this pilot study, we investigate the possible exploitability of circulating micro-RNAs (miRNAs) to track chronic heart failure (CHF) occurrence, and progression from NYHA class I to IV. (2)Methods: We screened 367 microRNAs using TaqMan microRNA Arrays in plasma samples from healthy controls (HC) and CHF NYHA-class I-to-IV patients (5/group). Validation was performed by singleplex assays on 10 HC and 61 CHF subjects. Differences in the expression of validated microRNAs were evaluated through analysis of covariance (ANCOVA). Associations between N-terminal pro-BNP (NT-proBNP), left ventricular end-diastolic volume (LVEDV) or peak oxygen uptake (VO2 peak) and plasma microRNA were assessed by multivariable linear regression analysis. (3)Results: Twelve microRNAs showed higher expression in CHF patients vs. HC. Seven microRNAs were associated with NT-proBNP concentration; of these, miR-423-5p was also an independent predictor of LVEDV. Moreover, miR-499-5p was a predictor of the VO2 peak. Finally, a cluster of 5 miRNAs discriminated New York Heart Association (NYHA) class-I from HC subjects. (4)Conclusions: Our data suggest that circulating miRNAs have the potential to serve as pathophysiology-based markers of HF status and progression, and as indicators of pre-symptomatic individuals.

Mortality Risk Factors in Patients who are in Heart Transplantation Waiting List

Purpose: to estimate the survival of patients in a heart transplantation waiting list (HTxWL) at V.A.Almazov NMRC from 2010 to 2017 and to define risk factors for death among these patients. Materials and methods: A single-centre retrospective study of 151 patients with advanced chronic heart failure (CHF) in HTxWL. Results and conclusion: Mortality in a HTxWL for the period 2010-2017 decreased. Based on the results of constructing the discriminant function, 4 factors predicting the survival of patients in HTxWL: ACE inhibitors/ARBs, beta-blockers, status 1 of UNOS, CHF NYHA class IV were isolated. The model has sufficient resolving power, but is not capable of predicting the outcome in the presence of acute decompensation of CHF.

Surgical treatment of patients with obstructive hypertrophic cardiomyopathy

To analyze in-hospital results of surgical treatment of patients with obstructive hypertrophic cardiomyopathy. There were 15 patients (8 women and 6 men) with obstructive hypertrophic cardiomyopathy and severe mitral insufficiency for the period from November 2017 to March 2019. Mean age of patients was 55.9±7.1 years. All patients had chronic heart failure NYHA class III and secondary coronary insufficiency. Surgical correction of LVOT obstruction and mitral valve repair with elimination of systolic anterior motion were technically successful in all cases. There was no need for mitral valve replacement in all patients. Heart failure NYHA class I-II in early postoperative period was observed in all cases. Careful preoperative planning with a comprehensive analysis of hemodynamic and anatomical features of LV and certain surgical experience are essential for adequate correction of LVOT obstruction without atrioventricular node injury and mitral valve repair.

Lung Ventilation Efficiency and Quality of Life After Orthotopic Heart Transplantation

The study involved 40 patients with terminal chronic heart failure (CHF) included in the waiting list for heart transplantation. Before surgery and after OHT all patients underwent cardiopulmonary exercise testing, evaluation of clinical status and quality of life (QL) according to the 36-Item Short Form Survey (SF-36). During the follow-up period (5 years) after OHT there were a significant increase in physical capacity, two-fold increase of peak oxygen consumption (VO2), normalization of VE/VCO2 slope level, improvement of the efficiency of the VO2 recovery within first minute and reduction of the VO2 recovery time. OHT was associated with significant improvement of physical and mental health components of QL. Among exercise test parameters significantly associated with improved physical health component of QL were increments in exercise capacity, peak VO2, rate of VO2 recovery within first minute. There was no relationship between cardiopulmonary parameters of exercise test and mental health component of QL. In patients with terminal CHF OHR led to significant increase of the lung ventilation efficiency and QL. Factors contributing to QL improvement after OHT were augmentation of left ventricular ejection fraction and reduction of CHF NYHA class. Among cardiopulmonary exercise test parameters, a high predictive value relative to improvement of subjective assessment of physical health component of QL showed exercise capacity, peak VO2, and efficiency of VO2 recovery within first minute.

Prognostic and symptomatic benefits with ivabradine: lessons from the SHIFT trial

Ivabradine, a funny current (If) inhibitor, has been developed for symptomatic therapy of angina and in chronic heart failure (CHF) with low ejection fraction. A large outcome trial, SHIFT (Systolic Heart Failure Treatment with the If inhibitor ivabradine trial), was conducted in patients with EF ≤ 35% in sinus rhythm and increased heart rate ≥70 b.p.m. It demonstrated that the addition of this new compound to the best possible contemporary therapy, including beta-blockers, was associated with a 18% relative risk reduction in the occurrence of cardiovascular mortality or hospitalization for worsening heart failure (HF), 26% relative risk reduction in HF hospitalization, and in HF death. This beneficial effect was of greater magnitude in patients with heart rate ≥75 b.p.m. Ivabradine improved health-related quality of life significantly and reduced the number of recurrent hospitalizations for HF. Sub-studies conducted in subgroups with important co-morbidities, i.e. chronic obstructive pulmonary disease, renal dysfunction, diabetes mellitus and low systolic blood pressure, show that the efficacy and the safety of the drug are similar compared with those observed in patients without these comorbidities. The acute cardiac effect is characterized by a reversal of the abnormal force–frequency relationship, thus resulting in preserved contractile function and increased stroke volume despite heart rate reduction. The chronic cardiac effect is characterized by a reverse remodelling of the left ventricle with reduced cardiac dimensions which result from unloading of the left ventricle. Ivabradine is now indicated in CHF NYHA class II–IV with systolic dysfunction in patients in sinus rhythm and whose heart rate is ≥75 b.p.m. in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contraindicated or not tolerated.

Delayed anthracycline-induced cardiomyopathy – case report

A 43-year-old man was admitted to the hematology department due to second recurrence of anaplastic lymphoma T-cell ALK+. Lymphoma was diagnosed 28 years earlier. The patient received COP regimen (17 cycles) and CHOP (5 cycles), radiotherapy and underwent splenectomy. He achieved complete remission at that time. Relapse of the disease was diagnosed 8 years later, which was treated with 6 cycles of chemotherapy (cytarabine, mitoxantrone, vepeside and glucocorticoids) and high-dose chemotherapy followed by hematopoietic stem cell transplantation. Second disease recurrence was found in 2013, it was anaplastic lymphoma T-cell ALK+ stage IIA by Ann Arbor. Echocardiography and myocardial perfusion scintigraphy revealed chronic heart failure NYHA class I. Angiotensin receptor antagonist (ramipril) and β-blocker (carvedilol) were recommended. The patient underwent 6 cycles of ESHAP, complete remission was reported after the second cycle. High-dose therapy with autologous stem cell rescue was considered at that time. However, having T-cell ALK+ lymphoma with a relatively good prognosis, previous prolonged complete remissions (respectively – 12 and 8 years), an insufficient yield from the harvest (3,33 × 106/kg CD34+ cells), heart failure and chronic active viral hepatitis B, the high risk intensive chemotherapy followed by hematopoietic stem cells transplantation was discontinued. The chemotherapy was complicated by brachial vein and superficial vein thrombosis of left upper limb and hypogammaglobulinemia. Follow-up echocardiography performed after completion of chemotherapy showed improvement in EF (64%).

Diastolic dysfunction in hypertrophic nonobstructive cardiomyopathy

The purpose of research was to assess the availability and prevalence of types of diastolic dysfunction of the left ventricle (LV) in hypertrophic nonobstructive cardiomyopathy (NHCM). 97 NHCM patients. Mean age 42.5 ± 14.9 years. Diastolic dysfunction assessed by Doppler echocardiography. Signs of chronic heart failure NYHA class I observed in 44 (45%) patients, class II--in 40 (41%), class II--in 13 (13%) patients. 83% patients had LVdiastolic dysfunction, mainly on the hypertrophic type. One third of the patients had pseudonormal type with uncertain interpretation. Diastolic dysfunction in terms of clinical manifestations determined mainly NYHA class III and syncope. Severity of LV diastolic dysfunction in NHCM depended on the severity of hypertrophy not only left, but the right ventricle too. In 94% of cases we observed not only diastolic dysfunction, but also reduction ofsecondary fibers shortening fraction--as sign of contractile dysfunction. Thus, in NHCM dominated diastolic dysfunction of hypertrophic type. Such dysfunction defining a clinic cardiac deficiency or syncope. One third of the patients had pseudonormal transmitral flow type, difficult to assess diastolic function. Diastolic dysfunction in NHCM was combined with impaired contractility of the walls of ventricle.

FACTORS EFFECTING THE DECOMPENSATION OF CHRONIC HEART FAILURE IN THE ELDERLY

Aim. To identify risk factors of decompensation of chronic heart failure (CHF) and related hospitalization in elderly outpatients. Material and methods. The total of 248 patients aged 60–85 years with CHF NYHA class II-IV were enrolled into the study. The first group consisted of 87 (35.1%) patients who required hospitalization due to CHF decompensation during the follow-up, the second group of 161 patients without need for hospital admission. All the patients had undergone clinical and laboratory examination, estimation of CHF severity by the Scale of clinical state, assessment of quality of life and 6-minute walk test (6MWT), echocardiography. Results. Patients were matched for age, gender, disability occurrence, education level, body mass index, quality of life, hemodynamic parameters, incidence rates of anemia, diabetes mellitus and atrial fibrillation. CHF was more severe in patients who had required hospitalization (p<0.001), they were more often diagnosed with left ventricular aneurysm (p=0.001), chronic kidney disease (p=0.001), left ventricular ejection fraction (LVEF)<35% (p<0.001), history of stroke (p<0.001), III-IV degree mitral regurgitation (p=0.007), hyperuricemia (p<0.001), lower exercise tolerance (p=0.007) compared with patients without hospitalization. Higher functional class of CHF (OR=0.29; 95% CI 0.13–0.69; p=0.003), LVEF<35% (OR 0.37; 95% CI 0.18–0.76; p=0.007), chronic kidney disease (OR=0.29; 95% CI 0.13–0.68; p=0.004) and hyperuricemia (OR=0.23; 95%CI 0.10–0.50; p<0.001) were shown to be independent risk factors of CHF decompensation that required hospital admission in elderly patients. Conclusuion. High FC of CHF, low LVEF, hyperuricemia and renal dysfunction play a key role in CHF decompensation and related hospitalization in elderly patients.

INFLUENCE OF QUINAPRIL ON THE REGULATORY-ADAPTIVE STATUS OF PATIENTS WITH CHRONIC HEART FAILURE HYHA CLASS I: RESULTS OF NOT COMPARATIVE STUDY

Aim. To assess effects of quinapril on the regulatory-adaptive status (RAS) in patients with chronic heart failure (CHF) NYHA class 1 and arterial hypertension (HT). Material and methods. Patients (n=49) with CHF NYHA class I and HT stage I–II (25 men and 24 women, aged 52.5±8.4 years) were included into an open noncomparative study. A cardio-respiratory synchronization (CRS) test, 6 minute walk test, treadmill test with evaluation of the maximal oxygen uptake during exercise, ambulatory blood pressure monitoring, echocardiography , determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasma level were performed at baseline and after 6 months of quinapril therapy. Results. The quinapril treatment (average daily dose 17.3±7.9 mg) improved myocardium structural and functional parameters, increased the exercise tolerance, reduced neurohumoral activity , improved the RAS according to CRS test: increase in synchronization range of cardiorespiratory cycles per minute from 8.0±2.1 to 11.0±2.5 (Δ27.3%; p<0.01), as well as RAS index from 52.6±7.8 to 89.7±8.9 (Δ41.4%; p<0.01), and decrease in the duration of CRS development at the minimal border of cardiac cycles from 15.5±3.5 to 12.9±2.8 (Δ15.8%; p<0.01). Conclusion. Quinapril has a positive effect on the RAS in patients with CHF NYHA class I and HT of stage I–II.

AB48-3: Triple site ventricular pacing for optimizing ventricular resynchronization: Design of the TRIP-HF study; technical feasibility

Cardiac Resynchronization Therapy (CRT) is usually achieved by pacing the two ventricles at one site each. Current evidence indicates that standard biventricular pacing (SBVP) fails at providing acceptable mechanical ventricular resynchronization (VR) in a large subset of CRT patients, especially those with very enlarged heart. We hypothesized triple-site biventricular pacing (TSVP) with two leads at the LV, would further optimize VR and thus improve global cardiac performance as compared with SBVP. The TRIP-HF (triple site biventricular pacing in heart failure is a single-blind randomized crossover study designed to compare TSVP and SBVP during two periods of 3-month each. Inclusion criteria were: chronic heart failure NYHA class III-IV, optimal medical treatment, permanent atrial fibrillation with slow ventricular rate to ensure permanent and complete ventricular capture by pacing, and LVEF≤35%. Patients were implanted with a CRT device connected to 3 ventricular leads. The two LV leads were placed in opposite position, preferably basal (LV1) and inferior-lateral (LV2). RV+LV2, and LV1 were connected to the ventricular and atrial ports of the device, respectively. DDDR and VVIR mode programming resulted in TSVP and SBVP, respectively. Between April 2003 and February 2005, 40 pts, mean age 70 ± 9 yrs, were included. 85% were in NYHA class III and 15% in class IV. ACE-inhibitors or ARB, beta-blockers and diuretics were given in 87%, 79% and 95%, respectively. The mean intrinsic QRS was 165 ± 42 ms. Mean LVEF was 26 ± 11%. 34 patients had the 3 leads implanted successfully (success rate: 85%) The mean implantation time was 139 min, with a mean fluoroscopy time of 31 min. Of the 6 failed attempts, one was related to coronary sinus dissection and the other 5 to unsuitable access/position for the LV lead. 4 pts were implanted with a SBVP system. No major adverse event occurred during the peri-operative period.

Antiinflammatory Effects of Cardiac Resynchronization Therapy in Patients with Chronic Heart Failure

Cardiac resynchronization therapy (CRT) pacing has been proposed as an additional treatment to medical therapy to improve heart failure patients with left ventricular asynchrony. The aim of this study was to evaluate the influence of CRT treatment on proinflammatory cytokines in patients with heart failure. Twenty patients, with a mean age 64 +/- 2 years, with severe chronic heart failure NYHA class II-IV (mean ejection fraction 25 +/- 2%), were included in the study. Patients were treated with CRT pacing, after failure of optimal therapy. Blood samples were taken at baseline, 3 months after pacing therapy, and after a subsequent 3-month period of no pacing for the assessment of proinflammatory cytokines TNF-alpha and its receptors (sTNFR-I, sTNFR-II), IL-6, adhesion molecules sICAM-1 and sVCAM-1, and the apoptotic indices sFas and sFas-Ligand. Levels of TNF-alpha, sTNFR-I, and sTNFR-II were reduced at the end of 3 months of CRT therapy and further reduced at the end of the no pacing period (P < 0.05, compared to baseline). Levels of IL-6 also declined after 3 months of CRT pacing (from 8.9 +/- 2.5 pg/mL to 4.7 +/- 1.3 pg/mL, P < 0.05) and this was maintained during the no pacing period (3.9 +/- 1.1 pg/mL P < 0.05 compared to baseline). The adhesion molecule sICAM-1 levels also reduced (from 265 +/- 17 ng/mL to 235 +/- 12, P < 0.05) after 3 months of CRT pacing and remained unchanged at the end of the no pacing period (219 +/- 12 ng/mL, P < 0.05 compared to baseline values). Major proinflammatory cytokines and the adhesion molecule sICAM-1 are reduced with CRT therapy and this effect is maintained for at least 3 months after discontinuation of pacing.

Ischemic etiology of heart failure identifies patients with more severely impaired exercise capacity

Background Peak oxygen uptake (peak VO2) and the regression slope of ventilation against CO2 production during exercise (VE/VCO2 slope) are powerful prognostic indicators in patients with chronic heart failure (CHF). Our purpose was to evaluate the influence of CHF etiology on peak VO2 and VE/VCO2 slope, independently of demographic, clinical, Doppler-echocardiographic and neurohormonal factors. Methods Data were collected from 239 CHF patients referred for a cardiopulmonary exercise test as part of their clinical evaluation. Patients were stratified according to their CHF etiology (ischemic versus non-ischemic). Results The etiology of heart failure was ischemic in 143 patients (60%) and non-ischemic in 96 (40%). Patients with ischemic etiology, compared with those with non-ischemic etiology, showed a lower peak VO2 (15.4±4.2 versus 17.8±4.8 ml/kg/min, p<0.0001) and a steeper VE/VCO2 slope (38.1±6.8 versus 34±5.3, p<0.0001). In the univariate model, age ( r=−0.36, p<0.0001), female sex ( r=−0.21, p=0.001), ischemic CHF etiology ( r=−0.26, p<0.0001) and NYHA class ( r=−0.52, p<0.0001) correlated with peak VO2. At multivariate analysis, ischemic CHF etiology ( β=−0.23, p=0.001) was a predictor of peak VO2 ( R 2=0.49) independently of age ( β=−0.23, p=0.001), female sex ( β=−0.25, p=0.0006) and NYHA class ( β=−0.31, p<0.0001). Similarly, ischemic etiology ( β=0.29, p=0.001) predicted the VE/VCO2 slope ( R 2=0.38) independently of E/A ratio ( β=0.27, p=0.01) and resting heart rate ( β=0.22, p=0.01). Conclusions Etiology of heart failure may influence the functional capacity and the ventilatory response to exercise.

1014-92 Impaired Microcirculation in Chronic Heart Failure

The microcirculation plays a crucial role in the exchange of oxygen, energy rich substrates and metabolites. The effects on the microcirculation of impaired heart function and disturbed peripheral skin circulation in chronic heart failure (CHF) are unknown. Nailfold capillary morphology and dynamics in CHF were studied in relation to parameters of left ventricular (LV) structure and function. Twenty patients (13 male, 7 female, age 64 ± 2 years) with CHF NYHA class II underwent a capillaroscopic examination at the finger nailfold using a computerised videophotometric system (Capiflow) at rest and after 1 min arterial occlusion. Patients were treated with diuretics, ACE inhibitors and digoxin and mean duration of symptoms was 65 ± 9 months. Study parameters were number, length, and diameter of the capillaries as well as capillary blood velocity (CBV). Further experiments included echocardiography and determination of LV ejection fraction by Tc-scintigraphy. Nailfold capillaries in established CHF are enlarged (afferent diameter 6.6 ± 0.4 μm, efferent diameter 8.2 ± 0.4 μm, ref. resp. &lt;6 and &lt;8 μm) and CBV is dramatically decreased (351 ± 64 μ/s, ref. &gt;600 μm/s at 23°C). The reactive hyperemic response to one minute arterial occlusion is attenuated (peak CBV 879 ± 158 μm/s, ref &gt; 2000 μm/s). CBV correlates positively with LV ejection fraction (r = 0.61, p = 001) and inversely with LV end-diastolic (r = -0.56, P = 0.04) and end-systolic (r = -0.69, P = 0.01) diameters. The time-to-peak flow (35 ± 5 s, ref. 6–10 s) after one min arterial occlusion is positively related (r = 0.68, P &lt; 0.05) to the duration of CHF. Our data indicate that microcirculation in chronic heart failure deteriorates in function of the severity and duration of heart failure.