Temporal trend and potential impact of angiotensin receptor neprilysin inhibitors on transcatheter edge-to-edge mitral valve repair.

INTRODUCTION AND OBJECTIVES: Transcatheter edge-to-edge repair (TEER) should be considered in patients with heart failure and secondary mitral regurgitation (MR). Angiotensin receptor-neprilysin inhibitors (ARNIs) have been demonstrated to improve prognosis in heart failure. We aimed to evaluate the impact ARNIs on patient selection and outcomes. METHODS: The population of the Spanish TEER prospective registry (March 2012 to January 2021) was divided into 2 groups: a) TEER before the ARNI era (n=450) and b) TEER after the recommendation of ARNIs by European Guidelines (n=639), with further analysis according to intake (n=52) or not (n=587) of ARNIs. RESULTS: A total of 1089 consecutive patients underwent TEER for secondary MR. In the ARNI era, there was a reduction in left ventricle dilation (82mL vs 100mL, P=.025), and better function (35% vs 38%, P=.011). At 2 years of follow-up, mortality (10.6% vs 17.3%, P <.001) and heart failure readmissions (16.6% vs 27.8%, P <.001) were lower in the ARNI era, but not recurrent MR. In the ARNI era, 1- and 2-year mortality were similar irrespective of ARNI intake but patients on ARNIs had a lower risk of readmission+mortality at 2 years (OR, 0.369; 95%CI, 0.137-0.992; P=.048), better NYHA class, and lower recurrence of MR III-IV (1.9% vs 14.3%, P=.011). CONCLUSIONS: Better patient selection for TEER has been achieved in the last few years with a parallel improvement in outcomes. The use of ARNIs was associated with a significant reduction in overall events, better NYHA class, and lower MR recurrence.

Acute Kidney Injury After Percutaneous Edge-to-Edge Mitral Repair.

BACKGROUND: In catheter-based procedures, acute kidney injury (AKI) is a frequent, serious complication ranging from 10% to 30%. In MitraClip (Abbott Vascular, Santa Clara, California), a usually contrast-free procedure, there is scarce data about its real incidence and impact. OBJECTIVES: This study aimed to evaluate incidence, predictive factors, and midterm outcomes of AKI in patients with significant mitral regurgitation (MR) undergoing transcatheter valve repair with MitraClip. METHODS: A total of 721 patients undergoing MitraClip were included. AKI was defined as an absolute or a relative increase in serum creatinine of >0.3 mg/dl or ≥50%, respectively, or the need for hemodialysis during index hospitalization. RESULTS: The mean age of the patients was 72 ± 11 years (28.3% women). Median estimated glomerular filtration rate (eGFR) was 43.7 ml/min/1.73 m2 (interquartile range: 30.9 to 60.1 ml/min/1.73 m2), and was <60 ml/min/1.73 m2 in 74.9% of the patients. AKI after MitraClip occurred in 106 patients (14.7%). Baseline hemoglobin (<11 g/dl) (odds ratio [OR]: 1.97; p = 0.003), urgent procedure (OR: 3.44; p = 0.003), and absence of device success (OR: 3.37; p < 0.001) were independent predictors of AKI. Patients with AKI had worse outcomes compared to those without AKI, including a higher proportion of in-hospital bleeding events (3.8% vs. 0.8%; p = 0.011), 2-year all-cause mortality (40.5% vs. 18.7%; p <0.001), and major adverse cardiac events (63.6% vs. 23.5%; p <0.001). Combination of AKI with significant residual MR after the procedure conferred even worst outcomes (2-year all-cause mortality 50.0% vs. 19.6%; p = 0.001, and major adverse cardiac events 70.0% vs. 18.9%; p < 0.001). CONCLUSIONS: Despite being a "zero-contrast" procedure, one-sixth of patients undergoing transcatheter mitral valve repair had AKI, linked to device failure or other severe conditions. The occurrence of AKI was associated with worse outcomes, highlighting the importance to detect and reduce this complication in high-risk population.

Clinical Outcomes and Prognosis Markers of Patients With Liver Disease Undergoing Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Analysis.

BACKGROUND: Chronic liver disease is a known risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Very little data exist about such patients treated with transcatheter aortic valve replacement (TAVR). Our objective was to evaluate early and late clinical outcomes in a large cohort of patients with liver disease undergoing TAVR and to determine predictive factors of mortality among these patients. METHODS AND RESULTS: This multicenter study collected data from 114 patients with chronic liver disease who underwent TAVR in 12 institutions. Perioperative and long-term outcomes were compared with a cohort of 1118 patients without liver disease after a propensity score-matching analysis (114 matched pairs). In-hospital mortality and vascular and bleeding complications were similar between matched groups. Acute kidney injury was more common in liver disease group (30.8% versus 13.5%; P=0.010). Although cardiovascular mortality was similar between groups (9.4% versus 6.5%; P=0.433) at 2-year follow-up, noncardiac mortality was higher in the liver group (26.4% versus 14.8%; P=0.034). Lower glomerular filtration rate (hazard ratio, 1.10, for each decrease of 5 mL/min in estimated glomerular filtration rate; 95% confidence interval, 1.03-1.17; P=0.005) and Child-Pugh class B or C (hazard ratio, 3.11; 95% confidence interval, 1.47-6.56; P=0.003) were the predictors of mortality in patients with chronic liver disease, with a mortality rate of 83.2% at 2-year follow-up in patients with both factors (estimated glomerular filtration rate <60 mL/min and Child-Pugh B or C). CONCLUSIONS: These findings suggested that TAVR is a feasible treatment for severe aortic stenosis in patients with early-stage liver disease or as bridge therapy before a curative treatment of the hepatic condition. Patients with Child-Pugh class B-C, especially in combination with renal impairment, had a very low survival rate, and TAVR should be carefully considered to avoid a futile treatment. These results may contribute to improve the clinical decision-making process and management in patients with liver disease.

Clinical impact of acute kidney injury on short- and long-term outcomes after transcatheter aortic valve implantation with the CoreValve prosthesis.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with increased mortality, but few data exist on the occurrence and clinical impact of AKI associated with transcatheter aortic valve implantation (TAVI). The objective of this study was to determine the incidence and prognosis of AKI after percutaneous implantation of the CoreValve(®) (Medtronic, Minneapolis, MN, USA) prosthesis. METHODS: A total of 357 patients with severe aortic stenosis and 9 patients with pure native aortic regurgitation were treated with the CoreValve prosthesis. AKI was defined according to Valve Academic Research Consortium criteria as the absolute increase in serum creatinine ≥0.3mg/dl at 72h post percutaneous procedure. RESULTS: AKI was identified in 58 patients (15.8%), none of whom required renal replacement therapy. In patients with AKI, the mortality at 30 days was 13.5% compared with 1.6% of patients without AKI, [odds ratio (OR)=12.2 (95% CI 3.53-41.9); p<0.001] and total mortality after a mean of 26.2±17 months was 29.3% vs. 14.9% [OR=2.36 (95% CI 1.23-4.51), p=0.008]. In the multivariate analysis, AKI was an independent predictor of cumulative total mortality [hazard ratio=2.151, (95% CI from 1.169 to 3.957), p=0.014]. CONCLUSIONS: The deterioration of renal function in patients undergoing TAVI with the CoreValve prosthesis is a serious and frequent complication. The occurrence of AKI was associated with increased early mortality and was also a predictor of worse outcomes in follow-up.

The Ibero-American transcatheter aortic valve implantation registry with the CoreValve prosthesis. Early and long-term results.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The aim of this study was to describe early experience and long-term follow-up with the CoreValve self-expanding aortic prosthesis at 42 Ibero-American hospitals. METHODS: Multiple centre observational study including 1220 consecutive patients with symptomatic severe aortic stenosis who are not suitable candidates for surgery and underwent transcatheter aortic valve implantation with the self-expanding Medtronic CoreValve System between December 2007 and May 2012. RESULTS: The registry included 1220 consecutive patients with a mean age of 80.8 ± 6.3 years and a mean logistic euroSCORE of 17.8% ± 13%. The procedural success rate was 96.1%. Hospital mortality was 7.3% and combined end-point was 21.3%. Aortic regurgitation after TAVI was present in 24.5% (Sellers grade ≥ 2). The estimated 1-year and 2-year survival rates were 82.1% and 73.4% respectively. The following issues were significant independent risk factors for hospital mortality: acute kidney failure (odds ratio 3.55); stroke (odds ratio 5.72); major bleeding (odds ratio 2.64) and euroSCORE (odds ratio 1.02). Long-term predictors of mortality were diabetes mellitus (hazard ratio 1.59, 95% confidence interval 1.09-2.31), severe chronic obstructive pulmonary disease (hazard ratio 1.85, 95% confidence interval 1.85-2.88), and functional classes NYHA III-IV (hazard ratio 1.31, 95% confidence interval 1.01-1.70). CONCLUSIONS: Transcatheter aortic valve implantation constitutes a safe and viable therapeutic option for high operative risk patients with severe aortic stenosis. Long-term prognosis is conditioned by associate comorbidities.

[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation]. / La extensión de la enfermedad coronaria determina la movilización de las células progenitoras endoteliales y las citocinas tras un primer infarto de miocardio con elevación del ST.

INTRODUCTION AND OBJECTIVES: Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. METHODS: We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. RESULTS: The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. CONCLUSIONS: Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission.

Influence of preinfarction angina on the release kinetics of endothelial progenitor cells and cytokines during the week after infarction.

BACKGROUND: Preinfarction angina, a possible form of ischaemic preconditioning, improves the prognosis in patients who experience a major ischaemic event; though the associated pathophysiology is not yet fully understood. The aim of this study was to determine the possible involvement of endothelial progenitor cells (EPC), the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF) in the development of preinfarction angina. METHODS AND RESULTS: We studied 41 patients (60·5 ± 12 years; 34% women) and 14 healthy controls; 43·9% of the patients had preinfarction angina. No differences were found in the baseline characteristics of the two groups. Although the EPC, VEGF and HGF were raised as compared with the control group, no significant differences were found according to the presence or absence of preinfarction angina in the levels of EPC (baseline, P = 0·25; day 3, P = 0·11; day 7, P = 0·32), VEGF (baseline, P = 0·96; day 3, P = 0·06; day 7, P = 0·57) or HGF (baseline, P = 0·18; day 3, P = 1; day 7, P = 0·86). An association was seen in the patients who had preinfarction angina between the EPC levels at baseline and on days 3 and 7 and the HGF on admission with the time from the angina to the STEMI (ß = -0·070; ß = -0·066; ß = -0·081; ß = -80·16; P < 0·05), showing a reduction in the level of EPC cells for each hour passed since the event. CONCLUSIONS: No differences were found in the release kinetics of EPC, VEGF or HGF after a first infarction according to whether the patients had angina during the week before the infarction.

Percutaneous treatment of a dysfunctional aortic bioprosthesis with the CoreValve(®) prosthesis.

Recently, percutaneous aortic valve replacement has emerged as a therapeutic option for patients with severe symptomatic aortic stenosis and a high surgical risk. We report our initial experience in four patients with percutaneous implantation of a CoreValve aortic prosthesis to treat aortic bioprosthesis dysfunction involving aortic stenosis or regurgitation. In-hospital and medium-term outcomes were analyzed. The procedure was performed under local anesthesia and guided by angiography. The prosthesis was implanted successfully in all patients, although a second prosthesis was required in one case because the first was positioned too high. There were no major complications. After a mean follow-up of 7 months (SD, 4.7), all patients remained asymptomatic.

Percutaneous implantation of the CoreValve self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain.

INTRODUCTION AND OBJECTIVES: The aim of the study was to describe early experience and medium-term follow-up with the CoreValve self-expanding aortic prosthesis at three Spanish hospitals. METHODS: The study included patients with severe symptomatic aortic stenosis. Other inclusion criteria were: aortic valve area <1 cm(2) (<0.6 cm(2)/m(2)); aortic valve annulus diameter in the range 20-27 mm; diameter of the ascending aorta at the level of the sinotubular junction < or = 40 mm (small prosthesis) or < or = 43 mm (large prosthesis), and femoral artery diameter >6 mm. RESULTS: The study included 108 patients with a mean age of 78.6 + or - 6.7 years, a mean aortic valve area of 0.63 + or - 0.2 cm(2) and a mean logistic EuroSCORE of 16% + or - 13.9% (range, 2.27%-86.4%). After valve implantation, the maximum echocardiographic transaortic valve gradient decreased from 83.8 + or - 23 to 12.6 + or - 6 mmHg. No patient presented with greater than grade-2 residual aortic regurgitation on angiography. The procedural success rate was 98.1%. No patient died during the procedure. Definitive pacemaker implantation was carried out for atrioventricular block in 38 patients (35.2%). At 30 days, all-cause mortality and the rate of the combined endpoint of death, stroke, myocardial infarction or referral for surgery were 7.4% and 8.3%, respectively. The estimated 1-year survival rate calculated using the Kaplan-Meier method was 82.3% (for a median follow-up period of 7.6 months). CONCLUSIONS: Our early experience indicates that percutaneous aortic valve replacement is a safe and practical therapeutic option for patients with severe aortic stenosis who are at a high surgical risk.

Comparison of medium-term outcomes obtained with drug-eluting stents and coronary artery bypass grafts in an unselected population of diabetic patients with multivessel coronary disease. Propensity score analysis.

INTRODUCTION AND OBJECTIVES: Since the introduction of drug-eluting stents, the optimum revascularization strategy in diabetic patients with multivessel coronary disease has remained controversial. METHODS: This study used multivariate logistic regression analysis and propensity score matching to compare results in 270 consecutive diabetic patients (2000-2004) with multivessel disease (> or =2 vessels with a >70% de novo stenosis involving the proximal left anterior descending coronary artery) who underwent either coronary artery bypass grafting (CABG; n=142) or implantation of a drug-eluting stent (DES; i.e. rapamycin or paclitaxel; n=128). The following clinical outcomes (i.e. major adverse cardiac or cerebrovascular events [MACCEs]) were assessed: death, nonfatal myocardial infarction (MI), stroke and repeat revascularization at 2 years. RESULTS: Patients who received DESs were older (67.5+/-7 years vs. 65.3+/-8 years; P=.05) and more often had a previous MI (49.2% vs. 28.2%; P< .01), but no more often had a depressed left ventricular ejection fraction < or =45% (32.4% vs. 28.1%). Coronary anatomy was more complex in surgical patients (SYNTAX score, 25.9+/-7 vs. 18.5+/-6; P< .001) and the quality of revascularization was better (i.e. anatomically complete revascularization: 52.8% vs. 28.1%; P< .01). The incidence of MACCEs was 18.7% in the CABG group and 21.8% in the DES group (adjusted odds ratio [OR] = 0.93; 95% confidence interval [CI], 0.47-1.86). The composite endpoint of death, MI or stroke occurred in 15.8% undergoing CABG and 12.9% receiving a DES (adjusted OR = 1.19; 95% CI, 0.72-1.88). There was less need for revascularization in CABG patients (4.3% vs. 12.1%; adjusted OR = 0.42; 95% CI, 0.16-1.14; P=.09). CONCLUSIONS: In an unselected population of diabetic patients with multivessel coronary disease, the principle advantage of CABG was the reduced need for revascularization. There was no difference in the rate of death, MI or stroke.

Closure of perivalvular leaks using an Amplatzer occluder.

Reoperation of patients with perivalvular leaks due to heart failure or hemolysis is associated with increased morbidity and mortality. Percutaneous closure using an Amplatzer device offers a promising alternative. We describe our initial experience between 2004 and 2006, during which we used an Amplatzer device in eight patients for the percutaneous closure of perivalvular leaks (four aortic and four mitral). The patients were all symptomatic and had a high surgical risk. Device placement was successful in all patients with mitral leaks and in three with aortic leaks. There were no periprocedural complications. With four of the seven (57%) device placements, there was a significant reduction in the degree of regurgitation and, at 12-month follow-up, only these four patients showed clinical improvements. Of the other three, one required reoperation and two died of non-cardiovascular causes. Percutaneous closure of perivalvular leaks was feasible and safe and can be regarded as a treatment option in patients with a high surgical risk.

Experiência inicial em Málaga(Espanha) com prótese aórtica CoreValve para tratamento de estenose aórtica sintomática grave / Malaga(Spain)early experience with the CoreValve aortic prosthesis for the treatment of severe symptomatic aortic stenosis

Introdução: A prevalência de estenose aórtica grave vem crescendo em decorrência do aumento da expectativa de vida. Alguns pacientes não se beneficiam do tratamento cirúrgico por causa das comorbidades associadas. Apresentamos os resultados de nossa experiência no tratamento percutâneo da estenose aórtica. Método: Estudo prospectivo, realizado entre abril de 2008 e fevereiro de 2009, em que 31 pacientes consecutivos com estenose aórtica grave sintomática e que apresentavam alto risco cirúrgico foram tratados com a prótese aórtica CoreValve. Todos os procedimentos foram realizados com anestesia local. Em 29 casos a via de acesso foi a artéria femoral, com introdutor 18 F, a punção femoral foi fechada com Prostar 10 F, e em 2 pacientes a artéria subclávia esquerda foi a via de acesso. Resultados: A média de idade foi de 77,8 ± 8,9anos e o EuroSCORE logístico médio foi de 17,5 ± 12,6%. O sucesso do implante foi de 100%. O gradiente de pico a pico após o implante desapareceu. Nenhum paciente apresentou insuficiência aórtica residual > grau 2 de Sellers. A mortalidade aos 30 dias foi de 3,2%. Foram necessários marca-passos definitivos em 31% dos pacientes. Depois de acompanhamento médio de 154 ± 90 dias, foram registrados 4 óbitos (1 morte súbita e 3 por causas não-cardíacas). Conclusões: O implante percutâneo da prótese aórtica CoreValve como tratamento alternativo da estenose aórtica grave em pacientes com alto risco cirúrgico é factível e seguro, com elevada taxa de êxito no procedimento e porcentual de complicações abaixo do esperado em função do risco cirúrgico estimado com o EuroSCORE.

Background: The prevalence of severe aortic stenosis is increasing with the rise in life expectancy. Some patients cannot undergo surgical treatment of aortic stenosis due to associated disorders. We present the results of our experience with the percutaneous treatment of aortic stenosis as an alternative to surgery in high-risk patients. Methods: This prospective cohort study included 31 consecutive high surgical risk patients with severe and symptomatic aortic stenosis treated with a CoreValve aortic prosthesis from April 2008 to February 2009. All the procedures were undertaken with local anesthesia. In 29 patients we used a femoral artery access, with an 18 F introducer, closing the femoral puncture with a 10 F Prostar, and in two patients the access was via the left subclavian artery. Results: The mean age of the patients was 77.8 ± 8.9 years and the mean logistic EuroSCORE was 17.5 ± 12.6%. The implant was successful in 100% of cases. The peak-to-peak gradient after the implant disappeared. No patient had residual aortic insufficiency Sellers' grade > 2. One-month mortality was 3.2%. A definitive pacemaker was required in 31% of the patients. After a mean follow-up of 154 ± 90 days there were four deaths (1 sudden death and 3 for noncardiac causes). Conclusions: Percutaneous implantation of the CoreValve aortic prosthesis as an alternative treatment for severe aortic stenosis in high surgical risk patients is feasible and safe, with a high success rate for the procedure and a percentage of complications below the expected for the surgical risk, as estimated by the EuroSCORE.

[Long-term prognosis in diabetic patients in whom revascularization is deferred following fractional flow reserve assessment]. / Pronóstico a largo plazo de diferir la intervención coronaria en diabéticos sobre la base de la reserva fraccional de flujo.

INTRODUCTION AND OBJECTIVES: The fractional flow reserve (FFR) has been shown to be a valid and useful measure in the functional assessment of coronary stenoses of intermediate severity. Our aim was to determine the usefulness of FFR assessment in diabetic patients, in whom determination of the FFR can be influenced by microvascular dysfunction. METHODS: Between 1997-2004, FFR assessment was used to evaluate 222 consecutive coronary lesions judged by an interventional cardiologist to be of intermediate severity (ie, 40%-70%). Intravenous adenosine (140 microg/kg per min) was used to achieve maximum hyperemia. The occurrence of cardiac events (ie, death, non-fatal acute myocardial infarction, and target lesion revascularization) was compared in diabetics and nondiabetics in whom FFR assessment gave a negative result and intervention was deferred. The mean follow-up period was 30+/-21 months. RESULTS: Revascularization was deferred for 144 lesions (in 136 patients) in which the FFR was >/=0.75. Of these, 42 lesions (29.2%) were in diabetics (40 patients). The proportion of patients who were female or who had hypertension, dyslipidemia or multivessel disease was greater in the diabetic group. There was no difference in indications for coronary angiography. In both groups, the most frequently investigated vessel was the left anterior descending coronary artery. The mean FFR was 0.87+/-0.06, and there was no difference between the groups. On long-term follow-up, there was no difference in the rate of death or acute myocardial infarction. Overall, 8.8% of nondiabetics and 14.3% of diabetics with a negative FFR test result required target lesion revascularization (P=.32). CONCLUSIONS: Our results indicate that deferring percutaneous coronary intervention in diabetics with a moderately severe coronary artery stenosis and an FFR >/=0.75 is safe.

[Transcatheter closure of aorto-left atrial fistula using an Amplatzer device]. / Cierre percutáneo de una fístula entre aorta y aurícula izquierda mediante dispositivo Amplatzer.

Aorto-left atrial fistulas are rare. We describe the case of a patient in whom transcatheter closure of an aorto-left atrial fistula was carried out using an Amplatzer septal occluder. The patient had previously undergone cardiac surgery twice because of a recurrent left atrial myxoma. Closure of this type of fistula using a transcatheter device should be considered when the location and size of the fistula are appropriate and there are no associated abnormalities. The risk of surgery must also be taken into account.