Jordi Pérez-Rodon

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.

Prognostic value of the electrocardiogram in patients with syncope: Data from the Group for Syncope Study in the Emergency Room (GESINUR)

BACKGROUND The Group for Syncope Study in the Emergency Room (GESINUR) was a Spanish multicenter, prospective, observational study that evaluated the clinical presentation and acute management of loss of consciousness in Spain. Several studies have shown that an abnormal ECG is a poor prognostic factor in patients with syncope. However, the prognostic significance of each ECG abnormality is not well known. OBJECTIVE The purpose of this study was to study the association between specific ECG abnormalities and mortality in patients with syncope from the GESINUR study. METHODS All patients in the GESINUR study who had syncope and had available, readable ECG and 12-month follow-up data were included in this retrospective observational study (n = 524, age 57 ± 22 years, 50.6% male). ECG abnormalities were analyzed and assessed to evaluate whether an association with all-cause mortality existed at 12 months. RESULTS ECGs were classified as abnormal in 344 patients (65.6%). Thirty-three patients died during follow-up (6.3%), but only 1 due to sudden cardiovascular death. Atrial fibrillation (odds ratio [OR] 6.8, 95% confidence interval [CI] 2.8-16.3, P <.001), intraventricular conduction disturbances (OR 3.8, 95% CI 1.7-8.3, P = .001), left ventricular hypertrophy ECG criteria (OR 6.3, 95% CI 1.5-26.3, P = .011), and ventricular pacing (OR 21.8, 95% CI 4.1-115.3, P <.001) were the only independent ECG predictors of all-cause mortality. CONCLUSION Although an abnormal ECG in patients with syncope is a common finding, only the presence of atrial fibrillation, intraventricular conduction disturbances, left ventricular hypertrophy ECG criteria, and ventricular pacing is associated with 1-year all-cause mortality.

Entrainment from the para-Hisian region for differentiating atrioventricular node reentrant tachycardia from orthodromic atrioventricular reentrant tachycardia

AIMS The difference between the stimulus-atrial and ventriculo-atrial intervals (SA-VA) and between the post-pacing interval and the tachycardia cycle length (PPI-TCL) during entrainment from the right ventricular apex distinguishes atrioventricular node reentrant (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT). We hypothesized that these features still apply when entrainment is performed from the para-Hisian region. METHODS AND RESULTS Forty-seven supraventricular tachycardias (34 AVNRT/13 AVRT) were included. The SA-VA and PPI-TCL were obtained in all patients by using two right-sided diagnostic catheters. In 24 of them, these measurements were also performed upon His-bundle capture during entrainment. A paced QRS widening of >or=40 ms during entrainment, when compared with the tachycardia QRS width, identified absence of His-bundle capture, P < 0.001. A SA-VA >75 ms distinguished AVNRT from AVRT, P < 0.001 (sensitivity/specificity 97%/100%). A PPI-TCL >100 ms was diagnostic of AVNRT, P < 0.001 (sensitivity/specificity 97%/92%). Upon His-bundle capture, the SA-VA and PPI-TCL shortened in AVNRT (121 +/- 23 to 66 +/- 24 ms; 139 +/- 30 to 85 +/- 31 ms, respectively, P < 0.001) and no longer differentiated AVNRT from AVRT. CONCLUSION Para-Hisian entrainment without His-bundle capture distinguishes AVNRT from AVRT with the advantage of using only two diagnostic catheters.

El síncope: un problema con mayúsculas

En este articulo se revisan algunos de los aspectos actuales y controvertidos sobre el sincope. En primer lugar, y de acuerdo con las nuevas guias de sincope de la Sociedad Europea de Cardiologia, se define el sincope, para diferenciarlo de otros cuadros que cursan con perdida transitoria de la conciencia. En segundo lugar, se hace una revision actualizada de la epidemiologia del sincope. Tambien se hacen unas consideraciones sobre el proceso diagnostico de los pacientes que sufren episodios de perdida transitoria de la conciencia, con especial enfasis en la estratificacion de riesgo. Por ultimo, se hace una revision actualizada del tratamiento de los pacientes con sincope, especialmente de las maniobras de contrapresion, y de las situaciones en que, debido al perfil de riesgo de los pacientes, se considere indicada la implantacion de un desfibrilador automatico, independientemente de la causa de los episodios sincopales.

Intra-atrial re-entrant tachycardia in congenital heart disease: types and relation of isthmus to atrial voltage

Background Intra-atrial re-entrant tachycardia (IART) is a frequent and severe complication in patients with congenital heart disease (CHD). Cavotricuspid isthmus (CTI)-related IART is the most frequent mechanism. However, due to fibrosis and surgical scars, non-CTI-related IART is also frequent. Objective The main objective of this study was to describe the types of IART and circuit locations and to define a cut-off value for unhealthy tissue in the atria. Methods and results This observational study included all consecutive patients with CHD who underwent a first ablation procedure for IART from January 2009 to December 2015 (94 patients, 39.4% female, age: 36.55 ± 14.9 years, 40.4% with highly complex cardiac disease). During the study, 114 IARTs were ablated (1.21 ± 0.41 IARTs per patient). Cavotricuspid isthmus-related IART was the only arrhythmia in 51% (n = 48) of patients, non-CTI-related IART was the only mechanism in 27.7% (n = 26), and 21.3% of patients (n = 20) presented both types of IART. In cases of non-CTI-related IART, the most frequent location of IART isthmus was the lateral or posterolateral wall of the venous atria, and a voltage cut-off value for unhealthy tissue in the atria of 0.5 mV identified 95.4% of IART isthmus locations. Conclusion In our population with a high proportion of complex CHD, CTI-related IART was the most frequent mechanism, although non-CTI-related IART was present in 49% of patients (alone or with concomitant CTI-related IART). A cut-off voltage of 0.5 mV could identify 95.4% of the substrates in non-CTI-related IART.

A risk score to predict the absence of left ventricular reverse remodeling: Implications for the timing of ICD implantation in primary prevention

BACKGROUND A prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3-6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR. METHODS Consecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up. RESULTS One hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81. CONCLUSIONS Pharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation.

QT Interval in Newborns of Different Ethnic Origin: Usefulness of Neonatal ECG Screening

The cost-effectiveness of neonatal electrocardiographic (ECG) screening has been questioned. The objective of this study was to establish normal values for the QT interval in newborns of different ethnic origin. Between 2005 and 2006, ECGs were obtained during the first 48 h of life from 1305 at-term newborns at the Hospital del Mar in Barcelona, Spain. The mean corrected QT interval (QTc) was 417.79+/-28.47 ms. A QTc longer than 440 ms was observed in 240 newborns (18.33%). The frequency of a pathologic QTc in Spanish newborns was 17.9%, compared with 27.7% in those of Maghreb or Near Eastern origin (P=.016), and 28.2% in those of Indian or Pakistani origin (P=.033). The QTc may vary for genetic reasons. A routine neonatal ECG is advisable only in ethnic groups in which the QTc is lengthened, to help counter the greater risk of sudden death in these infants.

Diagnostic Yield and Economic Assessment of a Diagnostic Protocol With Systematic Use of an External Loop Recorder for Patients With Palpitations

INTRODUCTION AND OBJECTIVES To assess the diagnostic yield and cost-effectiveness of a diagnostic protocol based on the systematic use of latest-generation external loop recorders (ELRs) compared with the classic diagnostic strategy for patients with recurrent unexplained palpitations. METHODS Two cohorts of consecutive patients referred for diagnosis of unexplained palpitations to the outpatient clinic of the arrhythmia unit were compared: a prospective cohort after the implementation of a new diagnostic protocol based on the systematic use of ELRs, and another, retrospective, cohort before the implementation of the protocol. The cost of diagnosis was calculated based on the number of complementary examinations, visits to outpatient clinics, or emergency department visits required to reach a diagnosis, and its costs according the prices published for the local health system. RESULTS One hundred and forty-nine patients were included (91 in the ELR group, 58 in the control group). The diagnostic yield was higher in the ELR group (79 [86.8%] definitive diagnoses in the ELR group vs 12 [20.7%] in the control group, P < .001). The cost per diagnosis was €375.13 in the ELR group and €5184.75 in the control group (P < .001). The cost-effectiveness study revealed that the systematic use of ELR resulted in a cost reduction of €11.30 for each percentage point of increase in diagnosis yield. CONCLUSIONS In patients with recurrent unexplained palpitations, evaluation by means of a study protocol that considers the systematic use of a latest-generation ELR increases diagnostic yield while reducing the cost per diagnosis.

Predictors of Acute Failure Ablation of Intra‐atrial Re‐entrant Tachycardia in Patients With Congenital Heart Disease: Cardiac Disease, Atypical Flutter, and Previous Atrial Fibrillation

Background Intra‐atrial re‐entrant tachycardia (IART) in patients with congenital heart disease (CHD) increases morbidity and mortality. Radiofrequency catheter ablation has evolved as the first‐line treatment. The aim of this study was to analyze the acute success and to identify predictors of failed IART radiofrequency catheter ablation in CHD. Methods and Results The observational study included all consecutive patients with CHD who underwent a first ablation procedure for IART at a single center from January 2009 to December 2015 (94 patients, 39.4% female, age: 36.55±14.9 years). In the first procedure, 114 IART were ablated (acute success: 74.6%; 1.21±0.41 IART per patient) with an acute success of 74.5%. Cavotricuspid isthmus–related IART was the only arrhythmia in 51%; non–cavotricuspid isthmus–related IART was the only mechanism in 27.7% and 21.3% of the patients had both types of IART. Predictors of acute radiofrequency catheter ablation failure were as follows: nonrelated cavotricuspid isthmus IART (odds ratio 7.3; confidence interval [CI], 1.9–17.9; P=0.04), previous atrial fibrillation (odds ratio 6.1; CI, 1.3–18.4; P=0.02), transposition of great arteries (odds ratio, 4.9; CI, 1.4–17.2; P=0.01) and systemic ventricle dilation (odds ratio 4.8; CI, 1.1–21.7; P=0.04) with an area under the receiver operating characteristic curve of 0.83±0.056 (CI, 0.74–0.93, P=0.001). After a mean follow‐up longer than 3.5 years, 78.3% of the patients were in sinus rhythm (33.1% of the patients required more than 1 radiofrequency catheter ablation procedure). Conclusions Although ablation in CHD is a challenging procedure, acute success of 75% can be achieved in moderate–highly complex CHD patients in a referral center. Predictors of failed ablation are IART different from cavotricuspid isthmus, previous atrial fibrillation, and markers of complex CHD (transposition of great arteries, systemic ventricle dilation).

Intra-atrial re-entrant tachycardia in patients with congenital heart disease: factors associated with disease severity

Aim Intra-atrial re-entrant tachycardia (IART) is a common complication in patients with congenital heart disease (CHD) and is related to increased morbidity and mortality. Few reports have been published about factors associated to IART severity. The aim of this study is to analyse factors associated to severe clinical presentation of IART. Methods and Results Observational study of all consecutive CHD patients who underwent a first IART ablation from January 2009 to December 2015 (94 patients, 39.4% female, and age: 36.55 ± 14.9 years). Severe clinical presentation was defined as heart failure, syncope, shock, electromechanical dissociation (EMD), or aborted sudden death. The majority of patients had moderately or highly complex cardiac defect (90.4%). Types of IART included cavotricuspid isthmus(CTI) dependent in 51% (48), non-CTI-related in 22.3% (20), and both types in 27.7% (26). In 38 patients (40.4%), a severe event occurred and in 16 (17%), the symptoms included shock, syncope, sudden death, or EMD. In 21 (22.3%), severe symptoms were the first manifestation of IART. In multivariate analysis, transposition of the great arteries (TGA) with right systemic ventricle (OR 5.32, 95% C.I. 1.6-7.02, P = 0.0005) and severe dilation of the venous atrium (VsA) (OR 4.17; 95% CI 1.4-8.12, P = 0.0009) were factors independently associated with severity. Conclusion In our series of 94 CHD patients with a high proportion of moderately to highly complex cardiac defects, severe consequences of IART were frequent. Transposition of the great arteries with systemic right ventricle and severe dilation of VsA were independently associated to severity. Early invasive procedures should be considered for these high-risk patients.