Circadian variability patterns predict and guide premature ventricular contraction ablation procedural inducibility and outcomes.

Background: Infrequent intraprocedural premature ventricular complexes (PVCs) may impede radiofrequency catheter ablation (RFA) outcome, and pharmacologic induction is unpredictable.

Objective: The purpose of this study was to determine whether PVC circadian variation could help predict drug response.

Methods: Consecutive patients referred for RFA with detailed Holter monitoring and frequent monomorphic PVCs were included.

Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period.

Background: Intrinsic cardiac nerve activity (ICNA) and skin nerve activity (SKNA) are both associated with cardiac arrhythmias in dogs.

Objective: The purpose of this study was to test the hypothesis that ICNA and SKNA correlate with postoperative cardiac arrhythmias in humans.

Methods: Eleven patients (mean age 60 ± 13 years; 4 women) were enrolled in this study.

Successful Delivery in a Patient With Left Ventricular Assist Device and Unplanned Pregnancy.

We report the case of a woman supported by a left ventricular assist device (LVAD) who presented at 20 weeks of gestation and decided against recommendations to continue with her pregnancy. This was managed with well-developed plan for a multidisciplinary team approach. With close and regular follow-up and regular adjustment of the patient's medications and LVAD parameters, successful delivery and outcome for both the mother and the newborn were achieved.

Recording sympathetic nerve activity from the skin.

Sympathetic tone is important in cardiac arrhythmogenesis; however, methods to estimate sympathetic tone are either invasive or require proper sinus node function that may be abnormal in disease states. Because of the direct and extensive connections among various nerve structures, it is possible for the sympathetic nerves in the various structures to activate simultaneously. Therefore, we hypothesized that nerve activity can be recorded from the skin and it can be used to estimate the cardiac sympathetic tone.

Small-Conductance Calcium-Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells.

Background: Purkinje cells (PCs) are important in cardiac arrhythmogenesis. Whether small-conductance calcium-activated potassium (SK) channels are present in PCs remains unclear. We tested the hypotheses that subtype 2 SK (SK2) channel proteins and apamin-sensitive SK currents are abundantly present in PCs.

Permanent nonselective His bundle pacing in an adult with L-transposition of the great arteries and complete AV block.

We report the placement of a permanent transvenous nonselective His bundle pacing lead in conjunction with a transvenous pacemaker/implantable cardioverter-defibrillator in an adult with Levo-Transposition of the Great Arteries (L-TGA) and a stenotic coronary sinus (CS) ostium, which would not accommodate a transvenous left ventricular (LV) pacing lead. Nonselective His bundle pacing provided a nearly identical ventricular activation pattern in this previously unpaced patient. Many L-TGA patients will have an eventual need for permanent pacing and, given the challenges of CS cannulation, His bundle pacing may represent a preferred modality rather than pure morphologic LV pacing or surgical systemic ventricular lead placement to achieve optimal electrical synchrony.

Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Objectives: We tested the hypothesis that oral progesterone administration attenuates drug-induced QT interval lengthening.

Background: Evidence from preclinical and human investigations suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening.

Methods: In this prospective, double-blind, crossover study, 19 healthy female volunteers (21-40 years) were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 49 days).

Validation and Utilization of a Clinical Next-Generation Sequencing Panel for Selected Cardiovascular Disorders.

The development of high-throughput technologies such as next-generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results.

Common genetic polymorphisms of adenosine A2A receptor do not influence response to regadenoson.

Aim: Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson.

Methods: Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled.

Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation.

Background: Skin sympathetic nerve activity (SKNA) is useful for estimating sympathetic tone in humans.

Objective: The purpose of this study was to test the hypotheses that (1) increased SKNA is associated with the onset and termination of paroxysmal atrial tachycardia (AT) and atrial fibrillation (AF) and (2) sinoatrial node response to SKNA is reduced in patients with more frequent AT or AF episodes.

Methods: SKNA and electrocardiogram were recorded in 11 patients (4 men and 7 women; average age 66 ± 10 years), including 3 patients with AT (11 ± 18 episodes per patient) and 8 patients with AF (24 ± 26 episodes per patient).

At the Heart of the Pregnancy: What Prenatal and Cardiovascular Genetic Counselors Need to Know about Maternal Heart Disease.

In the last decade, an increasing number of cardiac conditions have been shown to have a genetic basis. Cardiovascular genetic counseling has emerged as a subspecialty aiming to identify unaffected at-risk individuals. An important sector of this at-risk population also includes expectant mothers, in whom unique clinical challenges may arise.

The Academic Medical System: Reinvention to Survive the Revolution in Health Care.

Academic medical centers (AMCs) are presently facing enormous challenges arising from a prospective decline in government funding for research and education, shifting payment models emphasizing efficiency and value, and increasing competition. Left unabated, these challenges will drive many AMCs to de-emphasize or forsake their core missions in an effort to survive. Stemming from a symposium held at the 2015 Scientific Sessions of the American College of Cardiology titled, "The Academic Medical Center of the Future," we propose a series of changes, including internal restructuring, system-wide partnership, and novel approaches to support research and education, that are designed to better position AMCs to compete and face their growing challenges in a manner that preserves their essential missions.

Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts.

Background: Ventricular fibrillation (VF) during heart failure is characterized by stable reentrant spiral waves (rotors). Apamin-sensitive small-conductance calcium-activated potassium currents () are heterogeneously upregulated in failing hearts. We hypothesized that influences the location and stability of rotors during VF.

MIB2 variants altering NOTCH signalling result in left ventricle hypertrabeculation/non-compaction and are associated with Ménétrier-like gastropathy.

We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, a premalignant gastric disorder with epithelial hyperplasia and enhanced EGFR signalling. Ménétrier disease is believed to be an acquired disorder, but its aetiology is unknown. In affected members, we found a missense p.

Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene.

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment.

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts.

Identification of subpopulations with distinct treatment benefit rate using the Bayesian tree.

Characterization of a subpopulation by the difference in marginal means of the outcome under the intervention and control may not be sufficient to provide informative guidance for individual decision and public policy making. Specifically, often we are interested in the treatment benefit rate (TBR), that is, the probability of benefitting an intervention in a meaningful way. For binary outcomes, TBR is the proportion that has "unfavorable" outcome under the control and "favorable" outcome under the intervention.

Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram.

Background: Sympathetic nerve activity is important to cardiac arrhythmogenesis.

Objective: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone.

Phospholamban is concentrated in the nuclear envelope of cardiomyocytes and involved in perinuclear/nuclear calcium handling.

Aims: Phospholamban (PLB) regulates the cardiac Ca-ATPase (SERCA2a) in sarcoplasmic reticulum (SR). However, the localization of PLB at subcellular sites outside the SR and possible contributions to Ca cycling remain unknown. We examined the intracellular distribution of PLB and tested whether a pool of PLB exists in the nuclear envelope (NE) that might regulate perinuclear/nuclear Ca (nCa) handling in cardiomyocytes (CMs).

Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs.

Background: Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia.

Objective: We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem.

Methods: We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording.

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown.

Risk stratification for sudden cardiac death in North America - current perspectives.

Sudden cardiac death (SCD) accounts for approximately 360,000 deaths annually in the United States, and is the cause of half of all cardiovascular deaths. In patients with severely depressed left ventricular ejection fraction (LVEF), implantable cardioverter-defibrillators (ICDs) have been shown to significantly reduce total mortality, but many factors beyond LVEF influence the relative benefit afforded by ICD implantation. In fact, among patients with prior myocardial infarction, approximately half of all SCDs occur in patients without severe LV dysfunction, and in analyses of large ICD trials, certain patient subgroups derive no benefit to ICD implantation despite having low LVEF, often due to competing non-arrhythmic mortality.

KCNN2 polymorphisms and cardiac tachyarrhythmias.

Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear.