Emerging Technologies in Cardiac Pacing.

Cardiac pacing to treat bradyarrhythmias has evolved in recent decades. Recognition that a substantial proportion of pacemaker-dependent patients can develop heart failure due to electrical and mechanical dyssynchrony from traditional right ventricular apical pacing has led to development of more physiologic pacing methods that better mimic normal cardiac conduction and provide synchronized ventricular contraction. Conventional biventricular pacing has been shown to benefit patients with heart failure and conduction system disease but can be limited by scarring and fibrosis. His bundle pacing and left bundle branch area pacing are novel techniques that can provide more physiologic ventricular activation as an alternative to conventional or biventricular pacing. Leadless pacing has emerged as another alternative pacing technique to overcome limitations in conventional transvenous pacemaker systems. Our objective is to review the evolution of cardiac pacing and explore these new advances in pacing strategies.

High predictive value of paced QRS frequency in verification of left bundle branch pacing.

BACKGROUND: Left bundle branch area pacing (LBBAP) is a newer technique to deliver more synchronous left ventricular activation. Several criteria have been proposed, but not fully validated, to confirm LBBAP during implantation of the pacing lead. Spectral analysis has been used to characterize the frequency components of the clinical QRS utilizing the Fourier transform algorithm. We hypothesized that higher frequency content of the paced QRS complex may show predictive value of successful LBBAP. METHODS: We evaluated 84 patients with ejection fraction > 50%, who underwent LBB lead placement (n = 42) using ≥ 1 current criteria and right ventricular midseptal (RVsp) lead placement (n = 42) from 2000 to 2022. Time frequency analysis (Matlab) was used to determine the frequency content of the paced QRS complex. The centroid frequency (CF), which is the weighted average QRS frequency, was calculated. RESULTS: Patients in RVsp group had a longer paced QRS duration (155.6 ± 28.0 vs 127.1 ± 17.2, p < 0.002) compared to the LBBAP group. Of all standard ECG leads, the paced QRS in V2 gave the greatest difference of the CF of the LBBAP group at 8.8 ± 1.6 Hz versus 5.7 ± 0.7 Hz of the RVsp group. This difference was significant by both univariate (p < 0.003) and multivariate (p < 0.010) analysis. Predictive value of the CF for successful LBB pacing in lead V2 was highest with an AUC of 0.98. The sensitivity and specificity were 88.1% and 97.6%, respectively. CONCLUSION: Spectral analysis predicts successful LBBAP with higher frequency content when compared to RVsp pacing. Given the limitations to the current criteria to confirm LBBAP, intraprocedural use of frequency content analysis of the paced QRS complex in patients may prove useful at verifying LBB capture if verified by prospective clinical trials.

Intra- and Postprocedural Multimodality Imaging in Atrial Fibrillation.

Multi-modality imaging plays critical roles during and after procedures associated with atrial fibrillation. Transesophageal echocardiography is an invaluable tool for left atrial appendage occlusion during the procedure and at follow-up. Both cardiac computed tomography and cardiac magnetic resonance contribute to postprocedural evaluation of pulmonary vein isolation ablation. The present review is the second of a 2-part series where we discuss the roles of cardiac imaging in the evaluation and management of patients with atrial fibrillation, focusing on intraprocedural and postprocedural assessment, including the clinical evidence and outcomes data supporting this future applications.

Preprocedural Multimodality Imaging in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased risk of heart failure, stroke, and death. In current medical practice, multimodality imaging is routinely used in the management of AF. Twenty-one years ago, the ACUTE trial (Assessment of Cardioversion Using Transesophageal Echocardiography) results were published, and the management of AF changed forever by incorporating transesophageal echocardiography guided cardioversion of patients in AF for the first time. Current applications of multimodality imaging in AF in 2022 include the use of transesophageal echocardiography and computed tomography before cardioversion to exclude left atrial thrombus and in left atrial appendage occlusion device implantation. Transesophageal echocardiography, cardiac computed tomography, and cardiac magnetic resonance are clinically used for AF ablation planning. The decision to use a particular imaging modality in AF is based on patient's characteristics, guideline recommendation, institutional preferences, expertise, and cost. In this first of 2-part review series, we discuss the preprocedural role of echocardiography, computed tomography, and cardiac magnetic resonance in the AF, with regard to their clinical applications, relevant outcomes data and unmet needs, and highlights future directions in this rapidly evolving field.

Losartan Mitigates Oxidative Stress in the Brains of Aged and Inflamed IL-10-/- Mice.

Chronic inflammation, oxidative stress, and dysregulation of the renin-angiotensin system are closely linked, and their crosstalk commonly contributes to age-related physical and cognitive decline. The primary dementia-protective benefits of Angiotensin II type 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, there is an independently regulated brain-specific renin-angiotensin system. Here, we examined the impact of 4 weeks of oral Losartan treatment on the brains of aged (100 weeks old) IL-10-/- mice, an animal model of chronic inflammation and frailty. Our data show that aged IL-10-/- mice have higher AT1R and Nitrotyrosine (oxidative stress marker) levels in their frontal cortex tissue but not in cerebellar or hippocampal tissue compared to age- and sex-matched wild type mice. Losartan treatment for 4 weeks is associated with lower AT1R protein level, Nitrotyrosine, and Tau protein in the frontal cortex of aged IL-10-/- mice. Our results highlight the impact of Losartan, an AT1R blocker commonly prescribed for treating high blood pressure, on the brain-specific angiotensin system and AT1R-linked downstream effects such as brain oxidative stress damage and Tau burden in a frailty mouse model.

Guide to functional mitral regurgitation: a contemporary review.

Functional mitral regurgitation (FMR) occurs in the absence of organic mitral valve (MV) disease and is a result of LV dysfunction due to ischemic vs. non ischemic etiologies. The prevalence of FMR is increasing, as 2.0-2.5 million people in the USA were diagnosed with FMR in 2000-and this number is expected to double to 4 million by 2030. FMR tends to develop in a significant number of patients after myocardial infarction (MI) and many develop heart failure (HF) subsequently with mortality rates ranging from 15-40% at 1 year. Therefore, there has been much interest and effort to develop optimized methods for quantifying and classifying the severity of FMR, as well as developing effective therapeutic interventions to improve outcomes in patients with significant FMR. Echocardiogram is typically the primary diagnostic method of assessment, however, there have been various technological advances including cardiac CT and cardiac MRI that can better guide quantification and management of this disease. Management of this disease is mostly aimed at optimizing left ventricular (LV) remodeling with surgical and transcatheter management gaining more popularity with recent times. The purpose of this paper is to provide a comprehensive review of the current evaluation methods and interventional strategies for FMR.

Functional capacity and quality of life in the postural tachycardia syndrome: A retrospective cross-sectional study.

BACKGROUND: Postural tachycardia syndrome (POTS) is a complex syndrome of orthostatic intolerance that significantly affects quality of life. The relationship between functional capacity, quality of life, and age remains poorly understood in this patient population. The purpose of this cross-sectional study was to assess the clinical and exercise characteristics of patients with POTS who underwent exercise stress testing as part of cardiac rehabilitation, and to evaluate the relationships between functional capacity with age and sex, as well as the relationship between functional capacity and quality of life. METHODS: We included 255 consecutive adult patients with the diagnosis of POTS, by tilt table testing, who underwent exercise stress testing between 2012 and 2017. Clinical and stress test data were obtained from electronic medical records. RESULTS: Of the 255 patients, 232 (91%) were women, with median age 33.5 years. Prevalence of traditional CAD risk factors was low (2% diabetes, 13% hypertension, 7% hyperlipidemia, and 26% smoking history). Mean resting BP was 114 ± 13 mmHg systolic, resting HR was 76 ± 13 bpm, METs achieved 9.2 ± 2.2, and 1 min HR recovery 32 ± 17 bpm. 113 patients (44%) had abnormal functional capacity for age and sex. When analyzed by age groups, younger POTS patients had increasingly lower than expected functional capacity (compared to predicted normals) than did older patients (ANOVA P = 0.0017). The SF-36 physical component of patients with abnormal functional capacity was significantly lower than those with normal functional capacity. (p = 0.006). CONCLUSIONS: In this large cohort, patients with POTS were predominantly female (91%) and relatively young. The novel findings are that younger patients with POTS were more likely to have lower-than-average functional capacity for their age and sex compared to older patients, and that abnormal functional capacity was associated with lower quality of life by SF-36 physical component.

Correction to: ST­segment changes during tilt table testing for postural tachycardia syndrome: correlation with exercise stress test results.

Unfortunately, the 3rd author name was incorrectly published in the original publication. The complete correct name is given below.

ST-segment changes during tilt table testing for postural tachycardia syndrome: correlation with exercise stress test results.

BACKGROUND: Prior studies have reported ECG (Electrocardiogram) changes during tilt table testing (TTT), specifically during repolarization with ST-segment and T-wave changes. The correlation with ischemic evaluation remains unclear. The purpose of this study was to analyze the prevalence of ST-segment changes during TTT in a young, otherwise healthy population of patients with postural tachycardia syndrome (POTS), and correlate them with exercise stress test results. METHODS: Two hundred and fifty-five patients with POTS who underwent TTT and an exercise treadmill test (ETT) were analyzed. RESULTS: Forty-five had ST-segment changes/depressions during TTT (91% female, average age 36 years). Of the 45, three had ST-segment depression during ETT; all three had negative exercise stress echocardiograms (ESEs). Two others had ST-segment depressions on ETT (but not TTT), with negative ESEs. CONCLUSION: In a cohort of young, female, otherwise healthy patients with POTS, ST-segment changes occurred in a significant portion (18%) of patients during TTT. When evaluated with exercise stress testing, these patients had no evidence of underlying ischemia on ETT or ESE.

Advances in MRI Applications to Diagnose and Manage Cardiomyopathies.

PURPOSE OF REVIEW: The prevalence of heart failure continues to rise, and imaging characterization of the cardiomyopathic process is important for identifying myocardial disease, initiating appropriate treatment, and improving outcomes. We aimed to summarize recent advances in cardiac magnetic resonance imaging (CMR) applications for the diagnosis, characterization, and implications on management of various cardiomyopathies. RECENT FINDINGS: Parametric mapping by CMR has emerged as an important advancement in quantification of myocardial fibrosis, increased extracellular space, and myocardial edema. In addition, improved assessment of myocardial function with myocardial strain assessment may provide early identification of patients at risk and determining responsiveness to therapeutic interventions. Novel MRI techniques and the advent of artificial intelligence may help to uncover important mechanistic insights into the cardiomyopathic process. Innovative CMR techniques continue to evolve, and it will be of interest to determine how these advances can be incorporated into clinical practice to improve diagnosis, treatment, and management of patients with cardiomyopathies.

Endothelin-1 as a therapeutic target in autosomal dominant polycystic kidney disease
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AIMS: Endothelin-1 (ET-1) is associated with the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD) via cyst progression. Elevated concentrations of ET-1 in ADPKD correlate with many phenotypic changes in the kidney such as renal cyst development, interstitial fibrosis, and glomerulosclerosis. In addition, an imbalance between renal ETA and ETB receptors possibly leads to more severe disease progression. The objective of this review is to determine whether evaluating the efficacy of these drugs in treatment of cystic kidney disease may be a worthwhile aim, as determined by results from animal and human models. MATERIALS AND METHODS: PubMed/Medline, Embase, and Google Scholar databases were searched using the key words "endothelin, endothelin-1 antagonists, and autosomal dominant polycystic kidney disease". All animal and human studies describing the effects of endothelin and endothelin-1 antagonists in ADPKD subjects were included in the review. RESULTS: Urinary ET-1 concentrations could serve as a noninvasive surrogate biomarker for kidney ET-1 levels, as it is inversely associated with eGFR, independent of age, sex, and blood pressure. Elevated urinary excretion of ET-1 may be a biomarker for early renal injury. Antagonization of ET-1 may hopefully be a novel therapy for slowing progression of kidney damage in ADPKD. CONCLUSION: Based on the literature reviewed in this manuscript, it is proposed that further research evaluating the efficacy of endothelin antagonists in treatment of cystic kidney disease is warranted. More human studies need to be performed with larger sample sizes. Therefore, the recommendation for treatment is inconclusive at this time.
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Radiation Therapy in the Management of Soft Tissue Sarcoma: A Clinician's Guide to Timing, Techniques, and Targets.

Radiation therapy represents a vital component in the multidisciplinary management of soft tissue sarcomas. Combined with limb-preserving surgery, radiation therapy represents a standard of care treatment option for patients with high-grade sarcomas. Radiation therapy for soft tissue sarcoma continues to evolve with changes in timing, techniques, and targets. Over the past 2 decades, increasing data have supported the role of preoperative radiotherapy with the potential for lower total doses of radiation and improved long-term function coming at the cost of increased wound complications for certain locations. Retroperitoneal sarcomas represent a location where preoperative treatment is becoming the standard of care based on anatomic constraints and challenges with delivering postoperative radiotherapy. Multiple radiation therapy techniques exist to deliver treatment; currently both 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy (IMRT) are appropriate options, although increasing data support the role of IMRT in reducing dose to critical structures (bone, bowel, kidneys, vessels) while maintaining target coverage. Traditional target volumes have included larger fields; however, recent prospective data have demonstrated that image guidance in conjunction with smaller treatment volumes may reduce toxicity while not increasing marginal failures, although follow-up is short. Because of the toxicity associated with treatment, novel radiotherapy strategies are being used such as stereotactic radiotherapy as well as the use of tumor genetics to identify patients most likely to benefit most from radiotherapy.

The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance.

Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox) homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS). A main rate-controlling step in RAS is renin, an enzyme that hydrolyzes angiotensinogen to generate angiotensin I. Angiotensin I is further converted to Angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II binds with equal affinity to two main angiotensin receptors-type 1 (AT1R) and type 2 (AT2R). The binding of Ang II to AT1R activates NADPH oxidase, which leads to increased generation of cytoplasmic reactive oxygen species (ROS). This Ang II-AT1R-NADPH-ROS signal triggers the opening of mitochondrial KATP channels and mitochondrial ROS production in a positive feedback loop. Furthermore, RAS has been implicated in the decrease of many of ROS scavenging enzymes, thereby leading to detrimental levels of free radicals in the cell. AT2R is less understood, but evidence supports an anti-oxidative and mitochondria-protective function for AT2R. The overlap between age related changes in RAS and mitochondria, and the consequences of this overlap on age-related diseases are quite complex. RAS dysregulation has been implicated in many pathological conditions due to its contribution to mitochondrial dysfunction. Decreased age-related, renal and cardiac mitochondrial dysfunction was seen in patients treated with angiotensin receptor blockers. The aim of this review is to: (a) report the most recent information elucidating the role of RAS in mitochondrial redox hemostasis and (b) discuss the effect of age-related activation of RAS on generation of free radicals.