More intensive CMV-infection in chronic heart failure patients contributes to higher T-lymphocyte differentiation degree.

Immunosenescence in chronic heart failure (CHF) is characterized by a high frequency of differentiated T-lymphocytes, contributing to an inflammatory status and a deficient ability to generate immunocompetent responses. CMV is the best known inducer of T-lymphocyte differentiation, and is associated with the phenomenon of immunosenescence. In this study, we included 58 elderly chronic heart failure patients (ECHF), 60 healthy elderly controls (HEC), 40 young chronic heart failure patients (YCHF) and 40 healthy young controls (HYC). High differentiation of CD8+ T-lymphocytes was found in CMV-seropositive patients; however, the differentiation of CD4+ T-lymphocytes was increased in CMV-seropositive but also in CHF patients. Anti-CMV antibody titers showed positive correlation with more differentiated CD4+ and CD8+ subsets and inverse correlation with CD4/CD8 ratio. Immunosenescence found in CHF patients is mainly due to the dynamics of CMV-infection, since the differentiation of T-lymphocyte subsets is related not only to CMV-infection, but also to anti-CMV antibody titers.

Analysis of early failure of Biotronik Linox Smart implantable cardioverter-defibrillator leads: A comparative study of three defibrillator leads.

BACKGROUND AND OBJECTIVES: Early failure of Biotronik Linox and Linox Smart leads (Biotronik, Berlin, Germany) has been reported in numerous recent publications. The aim of this study was to assess the performance of this lead compared with that of two other contemporary leads. METHODS: We conducted an ambispective study of all consecutive first implantations of defibrillator leads carried out in our center: Endotak (model 148, 158, Boston Scientific, Marlborough, MA, USA) (n = 173), Sprint Quattro (model 6644, 6947, Medtronic, Dublin, Ireland) (n = 145), and Linox Smart (Biotronik, model SD 65/16) (n = 120). RESULTS: During a median follow-up of 4.6 ± 2.1 years, failure occurred in nine Linox Smart (7.5%), one Endotak Reliance (0.6%), and no Sprint Quattro leads. The survival probability of the Linox Smart group was significantly lower than that of the Endotak and Sprint Quattro groups measured by the log-rank test (Linox vs Endotak; P < 0.001 and Linox vs Sprint Quattro; P < 0.001). Nonphysiological signals not due to external interference were observed in all Linox Smart leads, with normal parameters and without visible anomalies on chest x-ray. CONCLUSIONS: In this single-center experience, the survival rate of Linox Smart leads was 88% at 5 years of follow-up, which was significantly lower than that of the other leads. Comprehensive vigilance of Linox Smart leads, including home monitoring, may be advisable to facilitate early detection of lead failure and avoid inappropriate shocks.

Self-expanding TAVI using the cusp overlap technique versus the traditional technique: electrocardiogram changes and 1-year cardiovascular outcomes.

INTRODUCTION AND OBJECTIVES: Transcatheter aortic valve implantation (TAVI) using the cusp overlap technique (COT) has shown a lower pacemaker implantation rate at 30 days. The objective of this study was to compare electrocardiogram changes and clinical outcomes between COT and the traditional technique (TT) at 1 year of follow-up. METHODS: Observational, retrospective, nonrandomized study of consecutive patients undergoing TAVI between January 2015 and January 2021. Patients were matched using a propensity score and the TT was compared with COT. The primary endpoints were electrocardiogram changes and a combined endpoint including pacemaker implantation, hospitalization, or cardiovascular death at 1 year. RESULTS: We included 254 patients. After propensity score matching, 184 patients (92 per group) remained. There were no statistically significant differences in baseline characteristics. At 1 year, COT patients showed a significant reduction in new onset left bundle branch block (49% vs 27%, P=.002) and less P wave (13.1±21.0 msec vs 5.47±12.5 msec; P=.003) and QRS prolongation (29.77±27.0 msec vs 16.38±25.4 msec, P <.001). COT was associated with a significant reduction in the occurrence of the primary endpoint (SHR, 0.39 [IC95%, 0.21-0.76]; P=.005). CONCLUSIONS: At 1 year of follow-up, COT reduced the incidence of new onset left bundle branch block and diminished QRS and P wave widening compared with the TT. COT was also associated with a statistically significant reduction in the occurrence of the combined primary cardiovascular endpoint.

Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. MATERIAL AND METHODS: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. RESULTS: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. CONCLUSIONS: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

[Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA Study]. / Factores de riesgo asociados a la calcificación valvular en pacientes con enfermedad renal crónica. Análisis del Estudio Nefrona.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. MATERIAL AND METHODS: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. RESULTS: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33ml/min with significant decrease to 30.9ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. CONCLUSIONS: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Frailty Assessment in a Cohort of Elderly Patients with Severe Symptomatic Aortic Stenosis: Insights from the FRailty Evaluation in Severe Aortic Stenosis (FRESAS) Registry.

BACKGROUND: Precise evaluation of the degree of frailty is a fundamental part of the global geriatric assessment that helps to avoid therapies that could be futile. Our main objective was to determine the prevalence of frailty in a specific consult of patients undergoing aortic valve replacement. METHODS: From May 2018 to February 2020, all consecutive patients ≥75 years old, with severe symptomatic aortic stenosis, undergoing valve replacement in the Principality of Asturias (Northern Spain) were evaluated. RESULTS: A total of 286 patients were assessed. The mean age was 84 ± 4.01 years old; 175 (61.2%) were female. The short performance physical battery score was 8.5 ± 2.4 and the prevalence of frailty was 19.6% (56 patients). In the multivariable analysis, age, Barthel index and atrial fibrillation were independent predictors of frailty. CONCLUSIONS: The prevalence of frailty in our sample patients undergoing aortic valve replacement, evaluated by a standardized protocol, was 19.6%.

Randomised evaluation of a novel biodegradable polymer-based sirolimus-eluting stent in ST-segment elevation myocardial infarction: the MASTER study.

AIMS: The MASTER study was designed to compare the performance of a new biodegradable polymer sirolimus-eluting stent (BP-SES) with a bare metal stent (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study was a prospective, randomised (3:1), controlled, single-blind multicentre trial that enrolled 500 STEMI patients within 24 hours of symptom onset during 2013-2015. Three hundred and seventy-five patients were treated with BP-SES and 125 with BMS. One hundred and four (104) randomised patients underwent angiographic follow-up at six months. The primary clinical endpoint was target vessel failure (TVF), defined as cardiac death, MI not clearly attributable to a non-target vessel, or clinically driven target vessel revascularisation (TVR) at 12 months. The primary angiographic endpoint was in-stent late lumen loss (LLL) at six months in the angiographic cohort. The major secondary endpoint for safety was a composite of all-cause death, recurrent MI, unplanned infarct-related artery revascularisation, stroke, definite stent thrombosis (ST) or major bleeding at one month. At 12 months, TVF had occurred in 6.1% of BP-SES and 14.4% of BMS patients (pnon-inferiority=0.0004), mainly driven by a higher rate of repeat revascularisation in BMS patients. The safety endpoint occurred in 3.5% of BP-SES and 7.2% of BMS patients (p=0.127). In-stent LLL demonstrated the superiority (p=0.0125) of BP-SES (0.09±0.43 mm) over BMS (0.79±0.67 mm). CONCLUSIONS: The study showed clinical non-inferiority and angiographic superiority of BP-SES versus a comparator BMS, suggesting that this novel DES may be a potential treatment option in STEMI.

Angiographic correlates of the treadmill scores in non-high-risk patients with unstable angina.

BACKGROUND: There has been no clear consensus regarding the optimum definition of a high-risk exercise ECG test. The aim of this study is to compare the diagnostic accuracy of several treadmill scores [American College of Cardiology/American Heart Association (ACC/AHA) High-Risk Criteria for exercise testing, Duke Treadmill Score, Veterans Affairs and West Virginia Prognostic Score, ST/Heart Rate Index] with the ST-segment depression analysis in the detection of significant and severe coronary disease as determined by coronary angiography. METHODS: The study included a cohort of 248 consecutive patients admitted to hospital for unstable angina. RESULTS: The sensitivities of the ACC/AHA High-Risk Criteria and the ST depression > or =1 mm were 89.02 and 76.83%, respectively, for the detection of significant coronary artery disease, and 96.15 and 86.54% for the detection of severe coronary artery disease. The specificities of the Duke Treadmill Score and the ST depression > or=1 mm were 96.43 and 73.81%, respectively, for the detection of significant coronary artery disease, and 81.63 and 47.45% for the detection of severe coronary artery disease. CONCLUSIONS: The ACC/AHA High-Risk Criteria and Duke Treadmill Score provided relevant diagnostic information not available from the ST segment analysis alone.

Early Everolimus Initiation Fails to Counteract the Cytotoxic Response Mediated by CD8+ T and NK Cells in Heart Transplant Patients.

The positive long-term effects of conversion to everolimus (EVL) after heart transplantation (HT) have been evaluated in several studies. However, the timing of EVL initiation, the best way to combine it with other immunosuppressive treatments, and the impact of these combinations on the immune response are poorly understood aspects. Here, we analyzed the immune phenotype and function of HT patients (n = 56) at short and long terms (prospective and retrospective cohorts), taking into account the time of EVL initiation: early (3 months post-transplant, EVL-E group) or late (>1 year post-transplant, EVL-L group) compared with mycophenolate mofetil treatment (MMF group). We show that early EVL conversion from MMF allows the increase of cytotoxic (CD56dim CD16+) NK and effector-memory (EM, CD45RA- CCR7-) CD8+ T cell subsets, which show a significantly higher level of expression of cytotoxic molecules, IFN-γ production and degranulation ability under activation. NK cell expansion is accompanied by an altered balance of receptor expression, increasing the activation state, and lytic activity of those cells. Those changes are detected after as little as 1 month after EVL conversion in association with the expansion of regulatory T cells and the decrease in B cell frequency. However, no changes in the immune cells subsets were observed after late EVL initiation (EVL-L) compared with the MMF group. Our results imply that only early EVL conversion induces key changes in the post-transplant immune response, preserving an efficient anti-viral response, but simultaneously showing a limited ability to counteract the cytotoxic response to the allograft.

Anomalous right coronary artery origin with interarterial pathway-importance of morphological origin assessment and the role of percutaneous interventionism.

Anomalies in coronary arteries (CA) are an important issue in cardiology and cardiovascular surgery. Specifically the anomalous origin of the right coronary artery (RCA) is of special importance because it is the most frequent anomaly. Clinical practice guidelines recommend the revascularization treatment in cases of interarterial pathway and documented myocardial ischemia and when hypoplasia, compression or obstruction is evident. We report two different cases of patients with anomalous origin of RCA and associated interarterial pathway. With them we want to highlight the different presentation forms of these patients and the different diagnostic alternatives available in each of the steps. In the patient with anomalous origin of the RCA and associated interarterial pathway, the first step after establishing the diagnosis is to rule out the presence of inducible ischemia. In those patients in whom ischemia induction tests are negative, the second step is to adequately assess the interarterial pathway, in order to rule out obstructions or compressions that also justify revascularization. In those cases in which all the tests are negative, the current evidence does not recommend revascularization, but adequate periodic follow-up is recommended. For this reason, we believe that the stress echocardiogram and exercise perfusion scintigraphy (based on availability and experience in each center) are fundamental because of their high sensitivity and specificity. We would also like to highlight the role that percutaneous interventionism can play in this type of clinical cases. Especially with patients of high surgical risk and in whom the percutaneous approach is feasible.

[Congenital coronary artery anomalies with origin in the contralateral sinus of Valsalva: which approach should we take?]. / Anomalías congénitas de las arterias coronarias con origen en el seno de Valsalva contralateral: qué actitud se debe seguir?

Recent years have witnessed a change in our perception of congenital coronary artery anomalies. From being regarded as simple coronary angiographic observations of little clinical significance, they have come to be seen as potential causes of sudden death in young people and of myocardial ischemia in adults. Diagnostic difficulties, a lack of knowledge about the mechanisms through which they produce myocardial ischemia, and their highly variable incidence have made congenital coronary artery anomalies of great interest to cardiologists. This article focuses on the group of coronary artery anomalies that is responsible for most clinical events: anomalies that have their origin in the contralateral sinus of Valsalva. Coronary artery anomalies are defined, their incidence is discussed, diagnostic criteria are given, and finally a treatment algorithm based on current knowledge is proposed.

Disease complexity in acute coronary syndrome is related to the patient's immunological status.

BACKGROUND: Our aim was to investigate whether patients with acute coronary syndrome (ACS) display an overall T cell immunosenescence that could be contributing to worsening the stage of the disease. METHODS AND RESULTS: We compared the immunological status of 52 ACS patients, 21 controls with absence of coronary artery disease (CAD) (C1), and 50 healthy individuals (C2). We characterized leukocyte and T lymphocyte subpopulations by flow cytometry. CAD was classified according to SYNTAX score, number of diseased coronary vessels, previous episodes of ACS and left ventricular ejection fraction (LVEF). ACS patients showed an increased number of total leukocytes, neutrophils and monocytes (p < 0.001), but a decreased number of lymphocytes (p < 0.05). ACS patients had significantly higher levels of NK cells and CD8+ T-cells (p < 0.05). ACS was associated with high differentiation in CD4+ and CD8+ T-lymphocytes. Frequencies of naïve, naïve CD31+, EM1, and pE1 subsets were significantly reduced in ACS patients (p < 0.05), while EM3, EM4 (in CD4+), and E (in CD8+) subsets were increased (p < 0.05). Aging of T-lymphocyte subpopulations was associated with a worse SYNTAX score (p < 0.05), and aging of CD4+ T-lymphocytes with a larger number of affected vessels, larger number of previous ACS episodes and lower LVEF, in ACS patients (p > 0.05). Furthermore, the proliferation ability of CD4+ and CD8+ T-lymphocytes was significantly impaired in ACS patients (p < 0.05), although they had increased activation (p < 0.05). CONCLUSIONS: We conclude that ACS patients show a higher degree of T-lymphocyte immunosenescence than healthy controls, which could contribute to disease impairment through a compromised adaptive immune response.

Transfemoral transcatheter aortic valve replacement compared with surgical replacement in patients with severe aortic stenosis and comparable risk: cost-utility and its determinants.

OBJECTIVE: To evaluate cost-effectiveness of transfemoral TAVR vs surgical replacement (SAVR) and its determinants in patients with severe symptomatic aortic stenosis and comparable risk. METHODS: Patients were prospectively recruited in 6 Spanish hospitals and followed up over one year. We estimated adjusted incremental cost-effectiveness ratio (ICER) (Euros per quality-adjusted life-year [QALY] gained) using a net-benefit approach and assessed the determinants of incremental net-benefit of TAVR vs SAVR. RESULTS: We analyzed data on 207 patients: 58, 87 and 62 in the Edwards SAPIEN (ES) TAVR, Medtronic-CoreValve (MC) TAVR and SAVR groups respectively. Average cost per patient of ES-TAVR was €8800 higher than SAVR and the gain in QALY was 0.036. The ICER was €148,525/QALY. The cost of MC-TAVR was €9729 higher than SAVR and the QALY difference was -0.011 (dominated). Results substantially changed in the following conditions: 1) in patients with high preoperative serum creatinine the ICERs were €18,302/QALY and €179,618/QALY for ES and MC-TAVR respectively; 2) a 30% reduction in the cost of TAVR devices decreased the ICER for ES-TAVR to €32,955/QALY; and 3) imputing hospitalization costs from other European countries leads to TAVR being dominant. CONCLUSIONS: In countries with relatively low health care costs TAVR is not likely to be cost-effective compared to SAVR in patients with intermediate risk for surgery, mainly because of the high cost of the valve compared to the cost of hospitalization. TAVR could be cost-effective in specific subgroups and in countries with higher hospitalization costs.

Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease.

BACKGROUND: Chronic heart failure (CHF) is characterized by an inflammatory status with high levels of cytokines such as IL-6. We hypothesized that patients with CHF may develop immunosenescence due to inflammation and that this may be associated with a worse stage of the disease. METHODS AND RESULTS: We compared the immunological features of 58 elderly CHF patients (ECHF), 40 young CHF patients (YCHF), 60 healthy elderly controls (HEC) and 40 healthy young controls (HYC). We characterized leukocyte and lymphocyte subpopulations by flow cytometry, and IL-6 concentration by ELISA. The extent of CHF was classified according to functional and/or morphological criteria: New York Heart Association functional class, AHA/ACC heart failure stages, left ventricular ejection fraction, and left ventricular hypertrophy. CHF patients showed an increased number of leukocytes, neutrophils and monocytes, but a decreased number of lymphocytes. CHF patients had significantly lower levels of B-cells and CD4+ T-cells, increased NK-cells in YCHF, and increased CD8+ T-cells only in ECHF. CHF was associated with high differentiation in CD4+ and CD8+ T-lymphocyte subsets. Aging of T-lymphocyte subpopulations and high IL-6 levels were associated with a worse clinical status. IL-6 also correlated positively with the number of highly differentiated T-lymphocytes and with their accelerated aging. CONCLUSIONS: We conclude that CHF patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and IL-6 levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system.