The Role of Genetics in Risk Stratification Strategy of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a heart disorder of diverse etiologies that affects millions of people worldwide, associated with increased mortality rate and high risk of sudden cardiac death. Patients with DCM are characterized by a wide range of clinical and pre-clinical phenotypes which are related with different outcomes. Dominant studies have failed to demonstrate the value of the left ventricular ejection fraction as the only indicator for patients' assessment and arrhythmic events prediction, thus making sudden cardiac death (SCD) risk stratification strategy improvement, more crucial than ever. The multifactorial two-step approach, examining non-invasive and invasive risk factors, represents an alternative process that enhances the accurate diagnosis and the individualization of patients' management. The role of genetic testing, regarding diagnosis and decision making, is of great importance, as pathogenic variants have been detected in several patients either they had a disease relative family history or not. At the same time there are specific genes mutations that have been associated with the prognosis of the disease. The aim of this review is to summarize the latest data regarding the genetic substrate of DCM and the value of genetic testing in patients' assessment and arrhythmic risk evaluation. Undoubtedly, the appropriate application of genetic testing and the thoughtful analysis of the results will contribute to the identification of patients who will receive major benefit from an implantable defibrillator as preventive treatment of SCD.

Cost, efficiency, and outcomes of pulsed field ablation vs thermal ablation for atrial fibrillation: A real-world study.

BACKGROUND: With the exponential growth of catheter ablation for atrial fibrillation (AF), there is increasing interest in associated health care costs. Pulsed field ablation (PFA) using a single-shot pentaspline multielectrode catheter has been shown to be safe and effective for AF ablation, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. OBJECTIVE: The purpose of this study was to compare cost, efficiency, effectiveness, and safety between PFA, CB, and RF for AF ablation. METHODS: We studied 707 consecutive patients (PFA: 208 [46.0%]; CB: 325 [29.4%]; RF: 174 [24.6%]) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, laboratory use, and hospital stay, and compared between ablation modalities, as were effectiveness and safety. RESULTS: Skin-to-skin times and catheter laboratory times were significantly shorter with PFA (68 and 102 minutes, respectively) than with CB (91 and 122 minutes) and RF (89 and 123 minutes) (P < .001). General anesthesia use differed across modalities (PFA 100%; CB 10.2%; RF 61.5%) (P < .001). Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and laboratory costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) than with CB (£8106) and RF (£8949) (P < .001). CONCLUSION: In this contemporary real-world study of the 3 major AF ablation modalities used concurrently, PFA had shorter skin-to-skin and catheter laboratory times than did CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely because of higher equipment cost.

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.

The effect of an mRNA vaccine against COVID-19 on endothelial function and arterial stiffness.

To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

Permanent pacemaker implantation in unexplained syncope patients with electrophysiology study-proven atrioventricular node disease.

OBJECTIVE: Syncope, whose cause is unknown after an initial assessment, has an uncertain prognosis. It is critical to identify patients at the highest risk who may require a pacemaker and to identify the cause of recurrent syncope to prescribe proper therapy. The aim of this study was to evaluate the effect of permanent pacing on the incidence of syncope in patients with unexplained syncope and electrophysiology study (EPS)-proven atrioventricular (AV) node disease. METHODS: This was an observational study based on a prospective registry of 236 consecutive patients (60.20 ± 18.66 years, 63.1% male, 60.04 ± 9.50 bpm) presenting with recurrent unexplained syncope attacks admitted to our hospital for invasive EPS. The decision to implant a permanent pacemaker was made in all cases by the attending physicians according to the results of the EPS. A total of 135 patients received the antibradycardia pacemaker (ABP), while 101 patients were declined. RESULTS: The mean of reported syncope episodes was 1.97 ± 1.10 (or presyncope 2.17 ± 1.50) before they were referred for a combined EP-guided diagnostic and therapeutic approach. Over a mean follow-up of approximately 4 years (49.19 ± 29.58 months), the primary outcome event (syncope) occurred in 31 of 236 patients (13.1%), and 6 of 135 (4.4%) patients in the ABP group as compared to 25 of 101 (24.8%) in the no pacemaker group (p < 0.001). CONCLUSION: Among patients with a history of unexplained syncope, a set of positivity criteria for the presence of EPS-defined AV node disease identifies a subset of patients who will benefit from permanent pacing.

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.

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.

The Mediterranean Diet Benefit on Cardiovascular Hemodynamics and Erectile Function in Chronic Heart Failure Male Patients by Decoding Central and Peripheral Vessel Rheology.

BACKGROUND: Mediterranean diet was evaluated on erectile performance and cardiovascular hemodynamics, in chronic heart failure patients. METHODS: 150 male stable heart failure patients were enrolled in the study (62 ± 10 years, New York Heart Association (NYHA) classes I-II, ejection fraction ≤40%). A detailed echocardiographic evaluation including estimation of the global longitudinal strain of the left ventricle and the systolic tissue doppler velocity of the tricuspid annulus was performed. Erectile dysfunction severity was assessed by the Sexual Health Inventory for Men-5 (SHIM-5) score. Adherence to the Mediterranean diet was evaluated by the MedDietScore. RESULTS: The SHIM-5 score was positively correlated with the MedDietScore (p = 0.006) and augmentation index (p = 0.031) and inversely correlated with age (p = 0.002). MedDietScore was negatively associated with intima-media-thickness (p < 0.001) and serum prolactin levels (p = 0.05). Multi-adjusted analysis revealed that the inverse relation of SHIM-5 and prolactin levels remained significant only among patients with low adherence to the Mediterranean diet (p = 0.012). CONCLUSION: Consumption of Mediterranean diet benefits cardiovascular hemodynamics, while suppressing serum prolactin levels. Such physiology may enhance erectile ability independently of the of the left ventricle ejection fraction.

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

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.