Carmen Adduci

Atrial Natriuretic Peptide Single Nucleotide Polymorphisms in Patients with Nonfamilial Structural Atrial Fibrillation

Background Atrial natriuretic peptide (ANP) has antihypertrophic and antifibrotic properties that are relevant to AF substrates. The -G664C and rs5065 ANP single nucleotide polymorphisms (SNP) have been described in association with clinical phenotypes, including hypertension and left ventricular hypertrophy. A recent study assessed the association of early AF and rs5065 SNPs in low-risk subjects. In a Caucasian population with moderate-to-high cardiovascular risk profile and structural AF, we conducted a case-control study to assess whether the ANP -G664C and rs5065 SNP associate with nonfamilial structural AF. Methods 168 patients with nonfamilial structural AF and 168 age- and sex-matched controls were recruited. The rs5065 and -G664C ANP SNPs were genotyped. Results The study population had a moderate-to-high cardiovascular risk profile with 86% having hypertension, 23% diabetes, 26% previous myocardial infarction, and 23% left ventricular systolic dysfunction. Patients with AF had greater left atrial diameter (44 ± 7 vs. 39 ± 5 mm; P < 0.001) and higher plasma NTproANP levels (6240 ± 5317 vs. 3649 ± 2946 pmol/mL; P < 0.01). Odds ratios (ORs) for rs5065 and -G664C gene variants were 1.1 (95% confidence interval [CI], 0.7-1.8; P = 0.71) and 1.2 (95% CI, 0.3-3.2; P = 0.79), respectively, indicating no association with AF. There were no differences in baseline clinical characteristics among carriers and noncarriers of the −664C and rs5065 minor allele variants. Conclusions We report lack of association between the rs5065 and -G664C ANP gene SNPs and AF in a Caucasian population of patients with structural AF. Further studies will clarify whether these or other ANP gene variants affect the risk of different subpheno-types of AF driven by distinct pathophysiological mechanisms.

Angiotensin Receptor Antagonists to Prevent Sudden Death in Heart Failure: Does the Dose Matter?

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.

Subcutaneous implantable cardioverter defibrillator eligibility according to a novel automated screening tool and agreement with the standard manual electrocardiographic morphology tool

PurposeSince subcutaneous implantable cardioverter defibrillator (S-ICD) introduction, the pre-implant screening based on a dedicated manual ECG tool (MST) was required to assure adequate sensing by the S-ICD. A novel automated screening tool (AST) has been recently developed. We assessed and compared the pass rate with AST and MST, and we measured the agreement between screening tools.MethodsThree electrodes were positioned at locations mimicking the placement of the S-ICD, and ECG recordings were collected in the supine and standing postures at rest. The three sensing vectors were analyzed with the MST and the AST. Eligibility was defined by the presence of at least one or two appropriate vectors in both postures.ResultsA total of 235 patients with an indication to ICD and no need for permanent pacing were enrolled. At least one suitable vector was identified in 214 (91%) patients with MST and 221 (94%) patients with AST (p = 0.219). At least two vectors were appropriate in 162 (69%) patients with MST and 187 (80%) patients with AST (p = 0.008). Overall, out of 1587 ECG analyzed, 1035 (65%) qualifying leads were identified with MST and 1111 (70%) with AST (p = 0.004). The agreement between the results of MST and AST ECG analysis was moderate (Kappa = 0.570; standard error = 0.022; CI = 0.526–0.613). The results were consistent regardless of the underlying cardiomyopathy. The most frequent reason for screening failure with MST was a high-amplitude T-wave (31% of failures). With AST, 23% of recordings that failed with MST for high-amplitude T-wave were classified as acceptable.ConclusionThe AST is associated with higher pass rate than the standard MST. It seems more tolerant of high-amplitude T-waves. Consequently, the agreement between MST and AST findings was only moderate.

New Oral Anticoagulants in Non-Valvular Atrial Fibrillation

Atrial fibrillation (AF) is associated with an increased risk of embolic stroke. Dose-adjusted vitamin K antagonists (VKAs) to a target international normalized ratio (INR) range of 2.0–3.0 reduce the risk of ischemic stroke and are currently recommended in all patients with AF at moderate-high risk for stroke or systemic embolism. However, VKAs have several drawbacks, including unpredictable anticoagulant response, food and drug interactions, need for regular laboratory monitoring and dose adjustment. These limitations prompted the introduction of new oral anticoagulants (NOA) that target thrombin and factor Xa, key-enzymes in the coagulation pathway. NOA have predictable pharmacodynamics, allowing fixed dosing without the need of laboratory monitoring, and have few drug and food interactions. The present review focuses on pharmacological properties, safety, and appropriate clinical use of dabigatran, rivaroxaban and apixaban.

Pulmonary hypertension and clinical correlates in hypertrophic cardiomyopathy

BACKGROUND Pulmonary hypertension (PH) in patients with hypertrophic cardiomyopathy (HCM) has been investigated in a small number of studies. Purpose of this study was to assess the prevalence and its association with outcome in a population of consecutive HCM outpatients. METHODS We retrospectively analyzed data of 361 consecutive HCM outpatients in whom echocardiographic measurements of pulmonary artery systolic pressure (PASP) were available at initial and most recent evaluation. Four different clinical groups were specifically investigated: patients without left ventricular outflow tract obstruction (group A, 165), with obstruction (group B, 126), patients diagnosed at the age≥65 (group C, 50) and patients with end stage (ES) HCM (group D, 20). RESULTS PH was identified in 41 (11.4%) of the 361 patients at initial evaluation while it has been recognized in 25 (7,8% [1.1%/year]) during a median follow-up of 3.4years. Analysis of subgroups showed that prevalence of PH increased from patient group A to D (8%, group A, 19%, group B, 28% group C, 70%, group D, respectively, p<0,01). During follow-up, patients with PH showed a significant higher HCM-related mortality (p=0.01) and morbidity (p<0.001) as compared with those without PH, but in multivariable analysis, PH resulted an independent risk factor only for HCM-related morbidity (HR=2.50, 95% CI 1.08-5.79, p=0.03). CONCLUSION PH affects a significant proportion of patients with HCM. Its prevalence varies according to different clinical profiles. It is associated with an unfavorable clinical outcome and is an independent predictor of morbidity.

Safety, Efficacy and Evidence Base for Use of the Subcutaneous Implantable Cardioverter Defibrillator

The trans-venous implantable cardioverter defibrillator (TV-ICD) is effective in treating life-threatening ventricular arrhythmia and reduces mortality in high-risk patients. However, there are significant short- and long-term complications that are associated with intravascular leads. These shortcomings are mostly relevant in young patients with long life expectancy and low risk of death from non-arrhythmic causes. Drawbacks of trans-venous leads recently led to the development of the entirely subcutaneous implantable cardioverter defibrillator (S-ICD). The S-ICD does not require vascular access or permanent intravascular defibrillation leads. Therefore, it is expected to overcome many complications associated with conventional ICDs. This review highlights data on safety and efficacy of the S-ICD and is envisioned to help in identifying the role of this device in clinical practice.

Premature ventricular extrastimulus without His or ventricular capture: An unexpected response during AV nodal reentrant tachycardia

A 52-year-old male was referred to our center for catheter ablation of recurrent episodes of paroxysmal supraventricular tachycardia. No relevant abnormalities were observed at his basal ECG and echocardiogram. Electrophysiological study was performed, and multipolar diagnostic catheters were introduced via the femoral veins. Typical atrioventricular (AV) nodal reentrant tachycardia with a medium rate of 200 bpm was reproducibly induced and diagnosed according to the standard criteria. During ventricular resetting maneuver using the His catheter, an expected phenomenon was observed after applying an early premature ventricular extrastimulus (PVE) (Figure 1). At a first look, the stimulus occurred during the ventricular refractory period without any capture. However, a phase of right bundle branch block (RBBB) occurred immediately after this apparently noncapturing PVE and without any subsequent change in the tachycardia cycle length making rate-dependent RBBB unlikely as a mechanism. The PVE did not capture ventricularmyocardium, nor theHis bundle (H-H intervals remained unchanged), and the tachycardia was not reset (Figure 1A). The induced RBBB was likely due to local concealed capture of the proximal RBB during its relative refractory period by the applied PVE. The stimulus could generate only an attenuated action potential with slow conduction in the RBB (the asterisk, Figure 1B) unable to advance the nextQRS. Nevertheless, the local capture of proximal RBB rendered it unexcitable by the antegrade activation of the ongoing tachycardia. Another possible mechanism is local electrotonus after PVE causing local loss of membrane potential adjacent to the distal RBB and resulting in conduction block of the advancing wave coming down the RBB. Subsequently, RBBB was likely maintained through a linking effect and repetitive retrograde penetration of the RBB by impulses propagating antegradely over the contralateral left bundle (Figure 1C). This case highlights intriguing electrophysiological phenomena that can still be observed during a classical pacing maneuver of a common reentry circuit including concealed capture of theHis-Purkinje system, electrotonus, linking effect, and functional aberrancy.

An unusual pattern of Para-Hisian pacing: The role of infra-Hisian conduction delay

A 26-year-old male athlete with a history of palpitations and intermittent preexcitation was referred to our center. The echocardiogram did not reveal any relevant abnormalities, while his basal 12-lead electrocardiogram showed sinus rhythm and incomplete left bundle branch block (LBBB). An electrophysiological study was performed, and multipolar diagnostic catheters were positioned at the His bundle (HB) region and coronary sinus. The AH and HV intervals were 60 milliseconds and 45 milliseconds, respectively. Retrograde conduction was concentric and decremental. During Para-Hisian pacing (PHP) maneuver, an interesting phenomenon was observed (Figure 1A). The loss of direct HB capture at a lower pacing-output led to delayed retrograde HB activation, with a subsequent significant and homogenous delay in atrial activation, consistent with a nodal response (beat 2, Figure 1A). The H-A interval was slightly shorter (∼10 milliseconds) at beat 2, likely because the loss of HB capture caused a marked prolongation of the H-H interval compared to the basal pacing cycle length favoring faster retrograde conduction over the AV node (ie, decremental conduction). However, the typical QRS widening was absent, and there was only a slight change in QRS morphology (earlier R/S transition in chest leads), while QRS duration remained nearly unchanged (∼120 milliseconds). Notably, the basal incomplete LBBB was observed to be more evident either spontaneously (Figure 1B), or at slightly faster rates of atrial pacing. Typically, direct HB capture at high pacing-output produces a narrower QRS because of the support of His-Purkinje system providing faster and more synchronous activation of both ventricles. In particular, the LBB should play a dominant role in this scenery since it supports the activation of the left ventricle (LV) that is far from the pacing site. In our case, the status of HB capture during PHP (direct capture vs. delayed retrograde activation) did not affect LV timing nor had a major effect on ventricular activation time (QRS duration), likely due to the basal conduction defect at the LBB level. In this study, no inducible tachycardia or accessory pathways were observed even at high-dose Isoproterenol and ablation was not performed. This case highlights an additional potential pitfall during PHP maneuver and how basal infra-Hisian conduction delay may affect the typical QRS changes that are essential criteria to recognize the status of HB capture. Multipolar HB recordings and the ability to detect retrograde HB potential, rather than relying on QRS changes, are the key for correct interpretation in such cases.

Supraventricular arrhythmia with discordant electrocardiographic features: What is the arrhythmia mechanism?

Junctional and AV nodal reentrant tachycardia share common electrocardiographic features, but they differ in their management and outcomes after catheter ablation. This case concerns a 60‐year‐old female who presented with recurrent episodes of a relatively slow, regular supraventricular arrhythmia. Electrocardiographic features of the arrhythmia were discordant regarding its underlying mechanism. However, careful analysis of 12‐lead electrocardiograms, with focus on the effect of spontaneous premature beats, pointed out the arrhythmia etiology. Electrophysiological study and pacing maneuvers defined the arrhythmic substrate that was successfully treated by catheter ablation.

Long-Term Left Ventricular Remodeling of Patients With Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV) remodeling carrying an adverse prognosis has been described. Conversely, a gradual and benign LV wall thinning has been suggested but never investigated. Therefore, we studied a HC cohort over a long period of time to evaluate the occurrence of a LV remodeling with a benign clinical course. Data of HC patients aged 18 to 65 years and without any condition known to influence LV remodeling were analyzed over a mean follow-up of 7.6 ± 5.7 years. Of 231 HC patients (65% males, mean age 46 ± 12 years), 47 (20%) developed LV remodeling, of whom 23 (10%) had a thinning ≥15% of LV maximal wall thickness from baseline without systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to 1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC-related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs 4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000 patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a benign outcome can occur over the long term in patients with HC. The prognostic importance of LV remodeling varies in relation to the different changes in LV morphology and function.