Bruno García del Blanco

Permanent Pacemaker Implantation After Transcatheter Aortic Valve Implantation Impact on Late Clinical Outcomes and Left Ventricular Function

Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P=0.013; R2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients.nnMethods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P =0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P =0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P =0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P =0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time ( P =0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P =0.013; R 2=0.121).nnConclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.nn# CLINICAL PERSPECTIVE {#article-title-43}

Late Cardiac Death in Patients Undergoing Transcatheter Aortic Valve Replacement Incidence and Predictors of Advanced Heart Failure and Sudden Cardiac Death

BACKGROUNDnLittle evidence exists of the burden and predictors of cardiac death after transcatheter aortic valve replacement (TAVR).nnnOBJECTIVESnThe purpose of this study was to assess the incidence and predictors of cardiac death from advanced heart failure (HF) and sudden cardiac death (SCD) in a large patient cohort undergoing TAVR.nnnMETHODSnThe study included a total of 3,726 patients who underwent TAVR using balloon (57%) or self-expandable (43%) valves. Causes of death were defined according to the Valve Academic Research Consortium-2.nnnRESULTSnAt a mean follow-up of 22 ± 18 months, 155 patients had died due to advanced HF (15.2% of total deaths, 46.1% of deaths from cardiac causes) and 57 had died due to SCD (5.6% of deaths, 16.9% of cardiac deaths). Baseline comorbidities (chronic obstructive pulmonary disease, atrial fibrillation, left ventricular ejection fraction ≤40%, lower mean transaortic gradient, pulmonary artery systolic pressure >60 mm Hg; p < 0.05 for all) and 2 procedural factors (transapical approach, hazard ratio [HR]: 2.38, 95% confidence interval [CI]: 1.60 to 3.54; p < 0.001; presence of moderate or severe aortic regurgitation after TAVR, HR: 2.79, 95% CI: 1.82 to 4.27; p < 0.001) independently predicted death from advanced HF. Left ventricular ejection fraction ≤40% (HR: 1.93, 95% CI: 1.05 to 3.55; p = 0.033) and new-onset persistent left bundle-branch block following TAVR (HR: 2.26, 95% CI: 1.23 to 4.14; p = 0.009) were independently associated with an increased risk of SCD. Patients with new-onset persistent left bundle-branch block and a QRS duration >160 ms had a greater SCD risk (HR: 4.78, 95% CI: 1.56 to 14.63; p = 0.006).nnnCONCLUSIONSnAdvanced HF and SCD accounted for two-thirds of cardiac deaths in patients after TAVR. Potentially modifiable or treatable factors leading to increased risk of mortality for HF and SCD were identified. Future studies should determine whether targeting these factors decreases the risk of cardiac death.

Impact of new-onset persistent left bundle branch block on late clinical outcomes in patients undergoing transcatheter aortic valve implantation with a balloon-expandable valve

OBJECTIVESnThe aim of this study was to determine the impact of new-onset persistent left bundle branch block (NOP-LBBB) on late outcomes after transcatheter aortic valve implantation (TAVI).nnnBACKGROUNDnThe impact of NOP-LBBB after TAVI remains controversial.nnnMETHODSnA total of 668 consecutive patients who underwent TAVI with a balloon-expandable valve without pre-existing LBBB or permanent pacemaker implantation (PPI) were included. Electrocardiograms were obtained at baseline, immediately after the procedure, and daily until hospital discharge. Patients were followed at 1, 6, and 12 months and yearly thereafter.nnnRESULTSnNew-onset LBBB occurred in 128 patients (19.2%) immediately after TAVI and persisted at hospital discharge in 79 patients (11.8%). At a median follow-up of 13 months (range 3 to 27 months), there were no differences in mortality rate between the NOP-LBBB and no NOP-LBBB groups (27.8% vs. 28.4%; adjusted-hazard ratio: 0.87 [95% confidence interval (CI): 0.55 to 1.37]; p = 0.54). There were no differences between groups regarding cardiovascular mortality (p = 0.82), sudden death (p = 0.87), rehospitalizations for all causes (p = 0.11), or heart failure (p = 0.55). NOP-LBBB was the only factor associated with an increased rate of PPI during the follow-up period (13.9% vs. 3.0%; hazard ratio: 4.29 [95% CI: 2.03 to 9.07], p < 0.001. NOP-LBBB was also associated with a lack of left ventricular ejection fraction improvement and poorer New York Heart Association functional class at follow-up (p < 0.02 for both).nnnCONCLUSIONSnNOP-LBBB occurred in ∼1 of 10 patients who had undergone TAVI with a balloon-expandable valve. NOP-LBBB was associated with a higher rate of PPI, a lack of improvement in left ventricular ejection fraction, and a poorer functional status, but did not increase the risk of global or cardiovascular mortality or rehospitalizations at 1-year follow-up.

Warfarin and Antiplatelet Therapy Versus Warfarin Alone for Treating Patients With Atrial Fibrillation Undergoing Transcatheter Aortic Valve Replacement

OBJECTIVESnThe study sought to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant atrial fibrillation (AF).nnnBACKGROUNDnGuidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) with a vitamin K antagonist (VKA) are scarce.nnnMETHODSnA multicenter evaluation comprising 621 patients with AF undergoing TAVR was undertaken. Post-TAVR prescriptions were used to determine the antithrombotic regimen used according to the following 2 groups: monotherapy (MT) with VKA (nxa0= 101) or multiple antithrombotic therapy (MAT) with VKA plus 1 or 2 antiplatelet agents (aspirin or clopidogrel; nxa0= 520). Endpoint definitions were in accordance with Valve Academic Research Consortium-2 criteria. The rate of stroke, major adverse cardiovascular events (stroke, myocardial infarction, or cardiovascular death), major or life-threatening bleeding events, and death were assessed by a Cox multivariate model regression survival analysis according to the antithrombotic regime used.nnnRESULTSnDuring a median follow-up of 13 months (interquartile range: 3 to 31 months) there were no differences between groups in the rate of stroke (MT: 5%, MAT: 5.2%; adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 0.45 to 3.48; pxa0= 0.67), major adverse cardiovascular events (MT: 13.9%, MAT: 16.3%; adjusted HR: 1.33; 95% CI: 0.75 to 2.36; pxa0=xa00.33), and death (MT 22.8%, MAT: 19.2%; adjusted HR: 0.93; 95% CI: 0.58 to 1.50; pxa0= 0.76). A higher risk of major or life-threatening bleeding was found in the MAT group (MT: 14.9%, MAT: 24.4%; adjusted HR: 1.85; 95% CI: 1.05 to 3.28; pxa0=xa00.04). These results remained similar when patients receiving VKA plus only 1 antiplatelet agent (nxa0= 463) were evaluated.nnnCONCLUSIONSnIn TAVR recipients prescribed VKA therapy for AF, concomitant antiplatelet therapy use appears not toxa0reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding.

Neurological damage after transcatheter aortic valve implantation compared with surgical aortic valve replacement in intermediate risk patients.

Background and purposeThe risk of neurological damage following transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) in severe aortic stenosis patients deemed to be at intermediate surgical risk is unknown. In this target population, the degree of neurological damage was compared using brain diffusion-weighted magnetic resonance imaging (DW-MRI) and cognitive testing.MethodsForty-six consecutive patients undergoing TAVI (78.0xa0±xa08.3 years; STS score 4.4xa0±xa01.7) and 37 patients undergoing SAVR (78.9xa0±xa06.2 years, STS score 4.7xa0±xa01.7) were compared. DW-MRI was performed in 67 patients (40 in TAVI vs. 27 in SAVR group) within the first 15xa0days post-procedure. A cognitive assessment was performed at baseline and at 3xa0months follow-up. The occurrence of potential cognitive impairment post-intervention was determined using the reliable change index (RCI).ResultsBaseline characteristics were comparable in TAVI and SAVR groups except for the presence of severe calcified aorta, which occurred more frequently in the TAVI group [17 (37xa0%) vs. 0 (0xa0%), pxa0<xa00.001]. Three patients presented a clinical stroke: 1 (2.2xa0%) in TAVI group vs. 2 (5.4xa0%) in SAVR group, (pxa0=xa00.58). No differences were observed in the rate of acute ischemic cerebral lesions detected by DWI in patients undergoing TAVI vs. SAVR [18 (45xa0%) in TAVI vs. 11 (40.7xa0%) in SAVR, adjusted OR 0.95; 95xa0% CI 0.25–3.65; pxa0=xa00.94]. TAVI was associated with a lower number of DWI lesions (adjusted OR 0.54; 95xa0% IC 0.37–0.79; pxa0=xa00.02). An older age was a predictor of the occurrence of acute lesions (OR 1.13; 95xa0% CI 1.03–1.23; pxa0=xa00.01), and the use of vitamin-K antagonist therapy had a protective effect (OR 0.25; 95xa0% CI 0.07–0.92; pxa0=xa00.037) regardless the type of intervention. Overall no significant changes were observed in global cognitive scores post-intervention (pxa0=xa00.23). The RCI showed mild cognitive decline in nine patients undergoing TAVI (26.4xa0%) and in six patients in the SAVR group (30.0xa0%) (pxa0=xa00.96). There was no association between the number and total volume of lesions and the occurrence of cognitive decline (CC Spearman 0.031, pxa0=xa00.85 and −0.011, pxa0=xa00.97, respectively).ConclusionsTAVI and SAVR were associated with a similar rate of acute silent ischemic cerebral lesions in intermediate risk patients. Although acute lesions occurred very frequently in both strategies, their cognitive impact was not clinically relevant.

Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Implantation: Impact on Late Clinical Outcomes and Left Ventricular Function

Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. Methods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P=0.013; R2=0.121). Conclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.Background— Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients.nnMethods and Results— A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74–1.30; P =0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56–1.17; P =0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77–1.30; P =0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11–0.85; P =0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time ( P =0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, −2.26; 95% confidence interval, −4.07 to −0.44; P =0.013; R 2=0.121).nnConclusions— The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.nn# CLINICAL PERSPECTIVE {#article-title-43}

Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling

Background Small and large preclinical animal models have shown that antagomir‐92a‐based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR‐92a inhibition in noncardiac organs prevents the translation of nonvectorized miR‐targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir‐92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should “acute” be added before “myocardial infarction” (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. Methods and Results In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir‐92a encapsulated in specific microspheres (9 μm poly‐d,‐lactide‐co‐glycolide [PLGA]) inhibited miR‐92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×‐fold inhibition at 1, 3, and 10 days). Downregulation of miR‐92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir‐92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall‐motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin‐PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). Conclusions Early single intracoronary administration of encapsulated antagomir‐92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.

Predictors and Impact of Myocardial Injury After Transcatheter Aortic Valve Replacement: A Multicenter Registry

BACKGROUNDnCardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown.nnnOBJECTIVESnThis study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR.nnnMETHODSnThis multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up.nnnRESULTSnOverall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (pxa0< 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (pxa0< 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (pxa0< 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (pxa0< 0.001).nnnCONCLUSIONSnSome degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK-MB levels associated withxa0greater acute and late mortality, imparting a negative impact on left ventricular function.

Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

BACKGROUNDnOral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events.nnnOBJECTIVEnThe MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications.nnnDESIGNnThe MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients.nnnCONCLUSIONSnThe MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications.

Cuantificación del área miocárdica en riesgo: validación de puntuaciones angiográficas coronarias con métodos de resonancia magnética cardiovascular

INTRODUCTION AND OBJECTIVESnQuantification of myocardial area-at-risk after acute myocardial infarction has major clinical implications and can be determined by cardiovascular magnetic resonance. The Bypass Angioplasty Revascularization Investigation Myocardial Jeopardy Index (BARI) and Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) angiographic scores have been widely used for rapid myocardial area-at-risk estimation but have not been directly validated. Our objective was to compare the myocardial area-at-risk estimated by BARI and APPROACH angiographic scores with those determined by cardiovascular magnetic resonance.nnnMETHODSnIn a prospective study, cardiovascular magnetic resonance was performed in 70 patients with a first successfully-reperfused ST-segment elevation acute myocardial infarction in the first week after percutaneous coronary intervention. Myocardial area-at-risk was obtained both by analysis of T2-short tau inversion recovery sequences and calculation of infarct endocardial surface area with late enhancement sequences. These results were compared with those of BARI and APPROACH scores.nnnRESULTSnBARI and APPROACH showed a statistically significant correlation with T2-short tau inversion recovery for myocardial area-at-risk estimation (BARI, intraclass correlation coefficient=0.72; P<.001; APPROACH, intraclass correlation coefficient=0.69; P<.001). Better correlations were observed for anterior acute myocardial infarction than for other locations (BARI, intraclass correlation coefficient=0.73 vs 0.63; APPROACH, intraclass correlation coefficient=0.68 vs 0.50). Infarct endocardial surface area showed a good correlation with both angiographic scores (BARI, intraclass correlation coefficient=0.72; P<.001; with APPROACH, intraclass correlation coefficient=0.70; P<.001).nnnCONCLUSIONSnBARI and APPROACH angiographic scores allow reliable estimation of myocardial area-at-risk in current clinical practice, particularly in anterior infarctions. Full English text available from:www.revespcardiol.org.