András Mihály Boros

Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients

Background Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT. Design We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months. Results RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0–12.8) vs. 19.5 (15.0–23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0–19.3) vs. 17.4 (10.5–22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15–0.90), p = 0.02 and HR = 0.42 (0.19–0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32–0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40–1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60–0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76–15.48), p = 0.003]. Conclusions Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation.

The ratio of the neutrophil leucocytes to the lymphocytes predicts the outcome after cardiac resynchronization therapy.

Abstract Aims The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). Methods and results The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12–4.05) vs. 2.21 (1.64–2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17–0.85), P = 0.01; NRI = 0.49 (0.14–0.83), P = 0.005; IDI = 0.04 (0.00–0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04–5.71), P = 0.03; NRI = 0.63 (0.24–1.01), P = 0.001; IDI = 0.04 (0.00–0.08), P = 0.02] independently of the NT-proBNP levels or other factors. Conclusion The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT.

Rationale and design of the BUDAPEST-CRT Upgrade Study: A prospective, randomized, multicentre clinical trial

Abstract Aims There is lack of conclusive evidence from randomized clinical trials on the efficacy and safety of upgrade to cardiac resynchronization therapy (CRT) in patients with implanted pacemakers (PM) or defibrillators (ICD) with reduced left ventricular ejection fraction (LVEF) and chronic heart failure (HF). The BUDAPEST-CRT Upgrade Study was designed to compare the efficacy and safety of CRT upgrade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular (RV) septal/apical pacing, reduced LVEF, and symptomatic HF. Methods and results The BUDAPEST-CRT study is a prospective, randomized, multicentre, investigator-sponsored clinical trial. A total of 360 subjects will be enrolled with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and a RV pacing ≥ 20%. Patients will be followed for 12 months. Randomization is performed in a 3:2 ratio (CRT-D vs. ICD). The primary composite endpoint is all-cause mortality, a first HF event, or less than 15% reduction in left ventricular (LV) end-systolic volume at 12 months. Secondary endpoints are all-cause mortality, all-cause mortality or HF event, and LV volume reduction at 12 months. Tertiary endpoints include changes in quality of life, NYHA functional class, 6 min walk test, natriuretic peptides, and safety outcomes. Conclusion The results of our prospective, randomized, multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator (CRT-D) upgrade in patients with symptomatic HF, reduced LVEF, and wide-paced QRS with intermittent or permanent RV pacing. Clinical trials.gov identifier NCT02270840.

Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Novel Biomarkers in Cardiac Resynchronization Therapy: Hepatocyte Growth Factor Is an Independent Predictor of Clinical Outcome

INTRODUCTION AND OBJECTIVES Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. METHODS We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. RESULTS Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P<.0001; integrated discrimination improvement=0.06; 95%CI, 0.02-0.11) and reverse remodelling (net reclassification improvement=0.39; 95%CI, 0.07-0.71; P=.01; integrated discrimination improvement=0.03; 95%CI, 0.00-0.06) resulted in a statistically significant reclassification and discrimination improvement. CONCLUSIONS Of the investigated biomarkers, only HGF predicted clinical outcomes following CRT independently of other parameters. Reclassification analyses showed that HGF measurements could be useful in refining patient selection.

Arteria iliaca aneurysma nyitott és endovascularis kezelése

Absztrakt: Bevezetes es celkitűzes: Az arteria iliaca aneurysmak az osszes aneurysmak 2%-at teszik ki. Optimalis kezelesuk nem egyertelmű, sebeszi kezelesuk eredmenyeiről alig all rendelkezesre hazai adat. Celkitűzesunk volt az arteria iliaca aneurysma miatt operalt betegek mortalitasanak es perioperativ morbiditasanak elemzese, valamint az elektiv nyitott műteten es stentgraft-implantacion (EVIAR) atesett betegcsoportok eredmenyeinek osszehasonlitasa. Modszer: Egy intezmenyben 2005. januar 1. es 2014. december 31. kozott arteria iliaca aneurysma miatt műteten atesett betegek retrospektiv vizsgalata. Eredmenyek: Tiz ev alatt 62 betegnel vegeztunk elektiv műtetet arteria iliaca aneurysma miatt (54 ferfi [87,1%]). A betegek atlageletkora 68,9 ev (19–89 ev) volt. Tiz esetben vegeztunk akut műtetet aneurysma ruptura miatt (13,9%), ezek kozul 3 beteg halt meg a perioperativ időszakban (30%). Az anatomiai lokalizaciot tekintve tobbsegeben az arteria iliaca communison (80,6%) alakult ki ertagulat. Elektiv beavat...

Application of “AL-FINE CRT” risk score before cardiac resynchronisation therapy implantation

The study by Kisiel et al. [1] retrospectively investigated the prognostic value of various parameters in 552 chronic heart failure patients undergoing cardiac resynchronisation therapy (CRT). The goal of the study was to set up a risk score system able to predict long-term mortality following CRT implantation and easily applicable in clinical practice. The main strength of the created score system, termed “AL-FINE CRT score” (Age [> 75 years], non-LBBB morphology [according to Strauss criteria], Furosemide dose [> 80 mg], Ischaemic aetiology, NYHA class (> III) and left ventricular EF [< 20%]), lies in the fact that its components can be easily obtained during the routine preimplantation check-up (medical history, physical examination, electrocardiography, and echocardiography) to assess the long-term mortality risk. The presence of any of the above variables equates to one point, so a maximum of six points could be achieved. Depending on the AL-FINE CRT score, the patients can be divided into three risk categories: low risk (0–1 points, five-year survival of approx. 80%), medium risk (2 points, five-year survival of approx. 60%), and high risk (3–6 points, five-year survival of approx. 40%). A high-risk score, according to the authors, should alert both the physician and the patient to evaluate the long-term benefit of the procedure more realistically and should identify those patients, in whom the implantation procedure might require more attention and maybe more experienced implanters in order to maximise the benefit [1]. The identified high-risk patients might also need “special care” following the implantation: more frequent follow-ups, strict device optimisation, multidisciplinary patient care, aggressive up-titration of medication, participation in rehabilitation programs, etc. Nevertheless, because the results are derived from a retrospective analysis, further prospective studies should validate the usefulness of the AL-FINE CRT model. Altogether there is a clear need to create applicable risk scores for patients who have undergone CRT implantation, to predict their long-term outcome. However, the validation and further assessment of the utility of such a score system are always challenging. A risk score system should not only be useful in risk prediction, but ideally it should also allow the clinicians to guide therapy or make therapeutic decisions, for instance regarding the choice of the device (implantable defibrillator [CRT-D] vs. pacemaker [CRT-P]), or the selection of pacemaker patients requiring CRT upgrade. To date, no such risk score systems exist, and the current guidelines do not clearly define the decision algorithm for the above processes [2, 3]. On the other hand, one should be cautious about relying on risk score systems alone, as an automated procedure, because the therapeutic decisions, circumstances of the implantation, and further device programming also have an impact on the long-term clinical outcome of patients; therefore, risk score systems are an additional, but not the sole component of the decision making process. The authors presented the overall discriminative power of the AL-FINE CRT model (C-statistics of 0.701), which corresponds to the requirements of cardiovascular risk models laid down by the American Heart Association [4]. This discriminative power of the AL-FINE CRT model is very similar to that of other risk models already tested in CRT (e.g. VALID-CRT score reported C-statistics of 0.700 and CRT-SCORE reported C-statistics of 0.748). While the presented risk score is useful in predicting the long-term clinical outcome, it has some weaknesses, such as the lack of procedure-related parameters, e.g. the targeted coronary sinus side branch or the activation delays between the right and left ventricular leads, which might also influence the outcome of patients after CRT implantation [5]. The presented results support the utility of the AL-FINE CRT model [6, 7] and emphasise its importance and application.

Quality of life measured with EuroQol-five dimensions questionnaire predicts long-term mortality, response, and reverse remodelling in cardiac resynchronization therapy patients

Abstract Aims There are previous studies on quality of life (QoL) in cardiac resynchronization therapy (CRT) patients; however, there are no data with the short EuroQol-five dimensions (EQ-5D) questionnaire predicting outcomes. We aimed to assess the predictive role of baseline QoL and QoL change at 6 months after CRT with EQ-5D on 5-year mortality and response. Methods and results In our prospective follow-up study, 130 heart failure (HF) patients undergoing CRT were enrolled. Clinical evaluation, echocardiography, and EQ-5D were performed at baseline and at 6 months of follow–up, continued to 5 years. Primary endpoint was all-cause mortality at 5 years. Secondary endpoints were (i) clinical response with at least one class improvement in New York Heart Association without HF hospitalization and (ii) reverse remodelling with 15% reduction in left ventricular end-systolic volume at 6 months. Fifty-four (41.5%) patients died during 5 years, 85 (65.3%) clinical responders were identified, and 63 patients (48.5%) had reverse remodelling. Baseline issues with mobility were associated with lower response [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.16–0.84; P = 0.018]. Lack of reverse remodelling correlated with self-care issues at baseline (OR 0.10, 95% CI 0.01–0.94; P = 0.04). Furthermore, self-care difficulties [hazard ratio (HR) 2.39, 95% CI 1.17–4.86; P = 0.01) or more anxiety (HR 1.51, 95% CI 1.00–2.26; P = 0.04) predicted worse long-term survival. At 6 months, mobility (HR 3.95, 95% CI 1.89–8.20; P < 0.001), self-care (HR 7.69, 95% CI 2.23–25.9; P = 0.001), or ≥ 10% visual analogue scale (VAS) (HR 2.24, 95% CI 1.27–3.94; P = 0.005) improvement anticipated better survival at 5 years. Conclusion EuroQol-five dimension is a simple method assessing QoL in CRT population. Mobility issues at baseline are associated with lower clinical response, whereas self-care issues predict lack of reverse remodelling. Problems with mobility or anxiety before CRT and persistent issues with mobility, self-care, and VAS scale at 6 months predict adverse outcome.

QUALITY OF LIFE MEASURED WITH EUROQOL-5D QUESTIONNAIRE PREDICTS LONG TERM MORTALITY AND ECHOCARDIOGRAPHIC RESPONSE IN CRT PATIENTS

Background: There are previous studies about the prognostic significance of quality of life (QoL) in CRT-implanted patients measured with complex heart failure questionnaires. However, there is no data with the EuroQol-5 Dimensions (EQ-5D) questionnaire, which provides a simple descriptive profile

Cardiac resynchronization therapy: current benefits and pitfalls

Cardiac resynchronisation therapy (CRT) has been shown to reduce all-cause mortality, heart failure events, and symptoms while improving exercise capacity and quality of life. Nevertheless, despite a large number of multicentre randomised trials and clear evidence confirming the above, there is still a higher number of patients who fail to develop reverse remodelling. In order to select the optimal patient population, the current European Society of Cardiology guidelines recommend a simultaneous evaluation of QRS morphology and width. However, based on recent data, QRS width itself is a less accurate parameter in the prediction of the outcome, as compared to QRS morphology. Furthermore, the baseline left ventricular (LV) ejection fraction (LVEF), which is also an known criterion for selecting CRT candidates (partly applied due to cost-benefit reasons), can be misleading. Data showed that patients with LVEF > 35% might also benefit from this type of treatment. Thus, LVEF should be evaluated less rigorously when screening patients for resynchronisation therapy. While the subsequent beneficial response to CRT is multifactorial, procedure-related parameters, such as LV lead position, are also crucial. The first data released recently confirmed the previous empiric clinical experience indicating that the LV lead should be implanted into the lateral or posterior coronary sinus side branch. This location was associated with a better long-term clinical outcome in terms of death and heart failure events. Some issues related to CRT are awaiting further clarification, such as the choice of the type of the implanted device (pacemaker or defibrillator) or the decision about CRT device upgrade. This review discusses the current evidence regarding the above, focusing on the questions that should be handled with caution or require clarification.