Best Practice Guide for Cryoballoon Ablation in Atrial Fibrillation: The Compilation Experience of More than 1000 Procedures.

Nowadays, the cryoballoon (CB) constitutes an established alternative to radio frequency (RF) ablation for pulmonary vein isolation (PVI), which offers the possibility to isolate the PVs with a single application. Since the introduction of the second-generation CB, we prospectively collected our data to optimize the procedure on >1000 consecutive patients who underwent CB PVI performed in our center. It is expected that subsequent guidelines will suggest first-line PVI through CB in patients with paroxysmal AF with a class I indication. Indeed, in the long-term follow-up (36 months) of the EARLY-AF trial, CB had a lower incidence of persistent atrial fibrillation episodes compared to the anti-arrhythmic drugs group. We now review the current best practices in an effort to drive consistent outcomes and minimize complications. PV isolation through CB is the most studied single-shot technique for atrial fibrillation ablation, having shown the potential to alter the natural history of the arrhythmia. Several procedural tips and tricks can improve procedural flow and effectiveness. In the present article we provided not only technical details but measurable biophysical parameters that can reliably guide the operator into achieving the best outcome for his patients.

Three-dimensional electroanatomically guided slow pathway elimination is associated with procedural improvements and clinical benefit in atrioventricular node reentrant tachycardia patients.

Background: Slow pathway (SP) ablation, in the context of atrioventricular node reentrant tachycardia (AVNRT) treatment could result in either complete elimination or only modification of the SP with ambiguity regarding associated benefits. Three-dimensional electroanatomical mapping (3D-EAM) may be used adjunctively aiming to complete SP elimination. Our purpose was to compare a 3D-EAM-based strategy targeting SP elimination to the conventional fluoroscopic approach with respect to clinical outcomes. Methods: One hundred and two consecutive AVNRT patients (36 males, mean age 53.2 ± 13.7 years) underwent in two successive periods a conventional fluoroscopic ablation approach (n = 42) or a 3D-EAM-guided ablation focusing on complete SP elimination (n = 60). Results: Several procedural parameters improved with 3D-EAM use, including fluoroscopy time (2.4 ± 4.7 min vs. 13 ± 4.5 min), dose-area product (1061 ± 3122 µGy × m2 vs. 5002 ± 3032 µGy × m2) and slow pathway elimination frequency (95% vs. 50%, all p < .001). Procedural time was slightly prolonged in the 3D-EAM group (101 ± 31 min vs. 87 ± 24 min, p = .013). Two major complications occurred in the conventional group. Altogether, over a mean follow-up of approximately 2.7 years, recurrence occurred in 6 of 42 (14.3%) in the conventional group as compared to 1 of 62 (1.7%) in the EAM-based group (p = .019). In the Kaplan-Meier analysis, time-to-event was significantly longer for the EAM-based patients (p < .030). Moreover, the EAM-based strategy was associated with less redo procedures' rates (9.5% in the non-EAM group vs. 0% in the EAM group, p = .026). Conclusions: The present study showed that an EAM-based SP elimination strategy is not only feasible and safe but it is also accompanied by improved clinical outcomes in the setting of AVNRT ablation.

Multipoint left ventricular pacing effects on hemodynamic parameters and functional status: HUMVEE single-arm clinical trial (NCT03189368).

OBJECTIVES: The aim of this study was to assess the capacity of optimized multipoint pacing (MPP) over optimized cardiac resynchronization therapy (CRT), in terms of clinical, functional, and echocardiographic parameters among patients with dyssynchronous heart failure (HF). METHODS: Eighty patients (Caucasian, 77.5% male, 68.4 ± 10.1 years, and 53.8% ischemic cardiomyopathy) sequentially received optimized CRT and optimized MPP over 6- and 12-month periods in a single-arm clinical trial. Clinical, laboratory, and echocardiographic assessment was conducted at baseline and after the completion of each step. RESULTS: Significant additive effects of optimized MPP over optimized CRT were noted with regard to 6-min walking distance (baseline/optCRT/optMPP: 293 ± 120 m vs 367 ± 94 m vs 405 ± 129 m and p < 0.001), NYHA class (2.36 vs 2.19 vs 1.45 and p < 0.001), VTIlvot (14.25 ± 3.2 cm vs 16.2 ± 4 cm vs 17.5 ± 3.4 cm and p < 0.001), stroke volume (48 ± 13.5 ml vs 55 ± 15 ml vs 59 ± 15 ml and p < 0.001), left ventricular ejection fraction (LVEF) (29% ± 7.1% vs 33% ± 7.3% vs 37% ± 7.7% and p < 0.001), maximal left atrial volume (77.2 ± 34.2 ml vs 74.2 ± 39.5 ml vs 67.7 ± 32 ml and p = 0.02), pulmonary artery systolic pressure (35.9 mmHg vs 33.5 mmHg vs 31 mmHg and p < 0.001), and right ventricular strain (-8.3% ± 6.9% vs -8.8% ± 6.6% vs -11.8% ± 6.1% and p = 0.022). With regard to VAC, stroke work (SW), and CP as percentages of maximal, there was a significant difference detected as compared to baseline for both CRT and MPP. Additive effects persisted only if suitable MPP dipoles were present. Exploratory analysis revealed that ischemic cardiomyopathy continued to exhibit significant differences that favor MPP, whereas nonischemic cardiomyopathy had similar findings with regard to total left atrial strain and quality of life. CONCLUSIONS: Optimized MPP showed significant improvements in hemodynamic parameters and ventricular function in patients with HF over optimized CRT. The beneficial effect was more prominent in men and in those with rather reduced LVEF, consistent with findings that suggest a beneficial trend in VAC and CP with more homogeneous depolarization offered by optimized MPP.

Multipoint left ventricular pacing as an addition to cardiac resynchronization therapy: a bridge to the holy grail?

Cardiac resynchronization therapy (CRT) constitutes a cornerstone to the treatment of advanced dyssynchronous heart failure (DyssHF); moreover it represents one of the few instances that a revolutionary approach was pursued, yielding previously unfathomable benefits to patients out of realistic therapeutic options. However, as is rather extensively established, nonresponse, or even negative response, to CRT continue to plague its course, precluding favourable effects in up to 40% of recipients, for a multitude of reasons. Given the scope of the issue of nonresponse, attempts to negate it by means of altering CRT delivery mode, and, more specifically, by introducing multipoint left ventricular pacing (MPP) have been focused on. Possible reasons for divergent trial results will be presented, as well as potential criteria for predicting whether MPP activation may reap additional benefits as compared to conventional biventricular pacing (BVP). Finally, an alternative framework for approaching CRT in general will be put forward, including advancements which in the (near) future may once more revolutionise heart failure treatment.

Comparative Trial of the Effects of Left Ventricular and Biventricular Pacing on Indices of Cardiac Function and Clinical Course of Patients With Heart Failure: Rationale and Design of the READAPT Randomized Trial.

Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Ventriculoarterial coupling (VAC) assesses energy efficiency of the failing heart and stroke work maximization for a given contractility, for both systemic and pulmonary circulations. Preferential left ventricular pacing (pLVP) can overcome iatrogenic right ventricular dysfunction by achieving left ventricle resynchronization and by allowing for intrinsic activation of the right side, with ramifications extending beyond cardiac output and atrial fibrillation occurrence. In the present article, we detail the design of a single-center randomized clinical trial to evaluate the effects of a pLVP algorithm. More specifically, following randomization of 220 CRT-eligible patients to standard biventricular pacing and pLVP, their clinical course will be followed for 12 months, through echocardiography to study indices of systolic and diastolic function of ventricles, left and right side VAC to evaluate efficiency, and cardiopulmonary exercise test to objectively document improvements in functional status, as well as a self-reported quality of life questionnaire. Device programming will be based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. Findings of this trial may provide evidence for alternative programming of the devices, linking pLVP to improved clinical outcomes.

The Role of Antithrombotic Therapy in Heart Failure.

Heart failure is a major contributor to global morbidity and mortality burden affecting approximately 1-2% of adults in developed countries, mounting to over 10% in individuals aged >70 years old. Heart failure is characterized by a prothrombotic state and increased rates of stroke and thromboembolism have been reported in heart failure patients compared with the general population. However, the impact of antithrombotic therapy on heart failure remains controversial. Administration of antiplatelet or anticoagulant therapy is the obvious (and well-established) choice in heart failure patients with cardiovascular comorbidity that necessitates their use, such as coronary artery disease or atrial fibrillation. In contrast, antithrombotic therapy has not demonstrated any clear benefit when administered for heart failure per se, i.e. with heart failure being the sole indication. Randomized studies have reported decreased stroke rates with warfarin use in patients with heart failure with reduced left ventricular ejection fraction, but at the expense of excessive bleeding. Non-vitamin K oral anticoagulants have shown a better safety profile in heart failure patients with atrial fibrillation compared with warfarin, however, current evidence about their role in heart failure with sinus rhythm is inconclusive and further research is needed. In the present review, we discuss the role of antithrombotic therapy in heart failure (beyond coronary artery disease), aiming to summarize evidence regarding the thrombotic risk and the role of antiplatelet and anticoagulant agents in patients with heart failure.

Antithrombotic Treatment after Atrial Fibrillation Ablation.

Atrial fibrillation is a major cause of debilitating strokes and anticoagulation is an established and indispensable therapy for reducing their rate. Ablation of the arrhythmia has emerged as a putative means of disrupting its natural course by isolating its triggers and modifying its substrate, dependent on the chosen method. An important dilemma lies in the need for continuation of anticoagulation therapy in those previously receiving it following an, apparently, successful intervention, purportedly preventing arrhythmia recurrence with considerably high rates. Current guidance, given scarcity of high-quality data from randomized trials, focuses on established knowledge and recommends anticoagulation continuation based solely on estimated thromboembolic risk. In the present review, it will be attempted to summarize the pathophysiological rationale for maintaining anticoagulation post-successful ablation, along with the latter's definition, including the two-fold effects of the procedure per se on thrombogenicity. Available evidence pointing to an overall clinical benefit of anticoagulation withdrawal following careful patient assessment will be discussed, including ongoing randomized trials aiming to offer definitive answers. Finally, the proposed mode of post-ablation anticoagulation will be presented, including the emerging, guideline-endorsed, role of direct oral anticoagulants in the field, altering cost/benefit ratio of anticoagulation and potentially affecting the very decision regarding its discontinuation.

What's in a prick? Vaccines and the cardiovascular system.

Evidence suggests a crucial role for vaccines in cardiovascular disease, mediated not only by disease prevention but also by immunomodulatory effects. This review attempts to briefly present the effects of pathogens and vaccines on the cardiovascular system and potential mechanisms for the development of vaccines against cardiovascular diseases per se. Current epidemiological evidence regarding vaccine effectiveness in different categories of heart disease is discussed, as well as current international guidelines' recommendations. In summary, cardiologists should strive to promote vaccination against specific pathogens with proven beneficial effects on cardiovascular diseases.

Comparison of left ventricular and biventricular pacing: Rationale and clinical implications.

Cardiac resynchronization therapy constitutes a cornerstone in advanced heart failure treatment, when there is evidence of dyssynchrony, especially by electrocardiography. However, it is plagued both by persistently high (~30%) rates of nonresponse and by deterioration of right ventricular function, owing to iatrogenic dyssynchrony in the context of persistent apical pacing to ensure delivery of biventricular pacing. Left ventricular pacing has long been considered an alternative to standard biventricular pacing and can be achieved as easily as inserting a single pacing electrode in the coronary sinus. Although monoventricular left ventricular pacing has been proven to yield comparable results with the standard biventricular modality, it is the advent of preferential left ventricular pacing, combining both the powerful resynchronization potential of multipolar coronary sinus and right-sided electrodes acting in concert and the ability to preserve intrinsic, physiological right ventricular activation. In this review, we aim to present the underlying principles and modes for delivering left ventricular pacing, as well as to highlight advantages of preferential over monoventricular configuration. Finally, current clinical evidence, following implementation of automated algorithms, regarding performance of left ventricular as compared with biventricular pacing will be discussed. It is expected that the field of preferential left ventricular pacing will grow significantly over the following years, and its combination with other advanced pacing modalities may promote clinical status and prognosis of patients with advanced dyssynchronous heart failure.

Cardiac Resynchronisation Therapy and Cellular Bioenergetics: Effects Beyond Chamber Mechanics.

Cardiac resynchronisation therapy is a cornerstone in the treatment of advanced dyssynchronous heart failure. However, despite its widespread clinical application, precise mechanisms through which it exerts its beneficial effects remain elusive. Several studies have pointed to a metabolic component suggesting that, both in concert with alterations in chamber mechanics and independently of them, resynchronisation reverses detrimental changes to cellular metabolism, increasing energy efficiency and metabolic reserve. These actions could partially account for the existence of responders that improve functionally but not echocardiographically. This article will attempt to summarise key components of cardiomyocyte metabolism in health and heart failure, with a focus on the dyssynchronous variant. Both chamber mechanics-related and -unrelated pathways of resynchronisation effects on bioenergetics - stemming from the ultramicroscopic level - and a possible common underlying mechanism relating mechanosensing to metabolism through the cytoskeleton will be presented. Improved insights regarding the cellular and molecular effects of resynchronisation on bioenergetics will promote our understanding of non-response, optimal device programming and lead to better patient care.

Biomarkers Associated with Atrial Fibrosis and Remodeling.

Atrial fibrillation is the most common rhythm disturbance encountered in clinical practice. Although often considered as solely arrhythmic in nature, current evidence has established that atrial myopathy constitutes both the substrate and the outcome of atrial fibrillation, thus initiating a vicious, self-perpetuating cycle. This myopathy is triggered by stress-induced (including pressure/volume overload, inflammation, oxidative stress) responses of atrial tissue, which in the long term become maladaptive, and combine elements of both structural, especially fibrosis, and electrical remodeling, with contemporary approaches yielding potentially useful biomarkers of these processes. Biomarker value becomes greater given the fact that they can both predict atrial fibrillation occurrence and treatment outcome. This mini-review will focus on the biomarkers of atrial remodeling (both electrical and structural) and fibrosis that have been validated in human studies, including biochemical, histological and imaging approaches.

QT Prolongation and Malignant Arrhythmia: How Serious a Problem?

QT prolongation constitutes one of the most frequently encountered electrical disorders of the myocardium. This is due not only to the presence of several associated congenital syndrome but also, and mainly, due to the QT-prolonging effects of several acquired conditions, such as ischaemia and heart failure, as well as multiple medications from widely different categories. Propensity of repolarization disturbances to arrhythmia appears to be inherent in the function of and electrophysiology of the myocardium. In the present review the issue of QT prolongation will be addressed in terms of pathophysiology, arrhythmogenesis, treatment and risk stratification approaches. Although already discussed in literature, it is hoped that the mechanistic approach of the present review will assist in improved understanding of the underlying changes in electrophysiology, as well as the rationale for current diagnostic and therapeutic approaches.

Effects of ventriculoarterial coupling changes on renal function, echocardiographic indices and energy efficiency in patients with acute decompensated systolic heart failure under furosemide and dopamine treatment: a comparison of three therapeutic protocols.

BACKGROUND: Ventriculoarterial coupling (VAC) status relates to tissue perfusion and its optimization may improve organ function and energy efficiency (EE) of the cardiovascular system. The effects of non-invasively calculated VAC improvement on echocardiographic parameters, renal function indices and EE improvement in patients with acute decompensated systolic heart failure were studied. Furthermore, effects of different treatment modalities on VAC, renal function and echocardiographic parameters were compared. METHODS: Systolic heart failure patients with ejection fraction <50% were studied, who, at the treating physician's discretion, received 8-hour infusions of: high dose furosemide (20mg/h), low dose furosemide (5mg/h) or dopamine (5µg/kg/min) combined with furosemide (5mg/h). Echocardiographic assessments were performed at 0 and 24h. Renal function was evaluated using serum creatinine and creatinine clearance. VAC and EE were assessed noninvasively, by echocardiography. RESULTS: Significant correlations were noted between VAC improvement and improvements in EE and serum creatinine (rho=0.96, p<0.001, rho=0.32, p=0.04 respectively). Dopamine-furosemide combination had a borderline effect on creatinine (p=0.08) and led to significant improvements in e', E/e' ratio (p=0.015 and p=0.009 respectively) and VAC (value closer to 1). CONCLUSION: VAC improvement correlated with EE and creatinine improvement, regardless of treatment, supporting a potential role for VAC status assessment and improvement in acute decompensated systolic heart failure. Dopamine and furosemide combination seemed to improve VAC and diastolic function but only had a borderline effect on renal function.

Brucella endocarditis as a late onset complication of brucellosis.

Brucella endocarditis (BE) is a rare but life threatening complication of brucellosis. We present a case report of a patient with relapsing brucellosis complicated with aortic valve endocarditis. The patient underwent valve replacement and required prolonged antibiotic treatment because of rupture of the noncoronary leaflet and development of congestive heart failure. Since the onset of endocarditis in patients with brucellosis is not known, proper follow-up is required in order to identify any late onset complications, especially in endemic areas.

Discriminating Between the Roles of Androgens and Estrogens in Cardiovascular Disease.

Cardiovascular disease shows a distinct difference in incidence rates between men and women, a fact that has been known for many years. While initial theories supported that this could be attributed to the protective effect of estrogens in women, attempts to correlate endogenous estrogen levels with cardiovascular risk factors and the progression of atherosclerosis-related indexes indicate otherwise. Similarly, endogenous androgen levels seem to correlate with opposite effects in males and females, whereas exogenous treatment with either androgens or estrogens fails to correspond to scientific expectations entirely. A brief discussion of the merits and pitfalls of placing either estrogens or androgens alone at the root of the problem shows that current understanding is inadequate concerning this major anthropological issue, as it refers to the primary global mortality and morbidity cause.

Sex steroids: beyond conventional dimorphism.

Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebrates to mammals and, last but not least, humans. Recognition of the various factors regulating sexual dimorphism initial establishment (i.e. sex determination and differentiation) and subsequent life-long adaptation to distinct functional and behavioural patterns has remained a hot topic for several decades. As our understanding of the various molecular pathways involved in this process increases, the significant role of sex steroids becomes more evident. At the same time, the recognition of new sites of steroid production (e.g. parts of the brain) and aromatization, as well as new target cells (owing to the proposed presence of additional receptors to those classically considered as primary steroid receptors) has lead to the need to revisit their spectrum of actions within a novel, multifactorial context. Thus, anthropology and medicine are presented with the challenge to unravel a major mystery, i.e. that of sexual orientation and differentiation and its potential contribution in human evolution and civilization development, taking advantage of the high-tech research tools provided by modern biotechnology. This short review summarizes the basic principles of sex determination and sex steroid function as they have been classically described in the literature and then proceeds to present examples of how modern research methods have started to offer a new insight on the more subtle details of this process, stressing that it is extending to virtually every single part and system of the body.