Novel approaches to define responders to interventional treatment in hypertension: insights from the SPYRAL HTN-OFF and HTN-ON MED trials.

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN "responders" prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN.

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF.

Background: The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood.

Objectives: The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI).

Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED.

Background: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations.

Methods: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs.

Long-term reduction in morning and nighttime blood pressure after renal denervation: 36-month results from SPYRAL HTN-ON MED trial.

Elevated morning and nighttime blood pressures (BP) are associated with increased risk of cardiovascular events such as stroke and myocardial infarction. We compared the long-term changes in morning and nighttime BP in patients with uncontrolled hypertension (office systolic BP between 150 and <180 mmHg/diastolic BP ≥ 90 mmHg; mean ambulatory systolic BP (SBP) between 140 and <170 mmHg; 1-3 prescribed antihypertensive medications). Eighty patients were randomized to RDN or sham control.

Translational value of preclinical models for renal denervation: a histological comparison of human versus porcine renal nerve anatomy.

Background: Preclinical models have provided key insights into the response of local tissues to radiofrequency (RF) renal denervation (RDN) that is unobtainable from human studies. However, the anatomic translatability of these models to the procedure in humans is incompletely understood.  Aims: We aimed to compare the renal arterial anatomy in normotensive pigs treated with RF-RDN to that of human cadavers to evaluate the suitability of normotensive pigs for determining the safety of RF-RDN.

Clinical event reductions in high-risk patients after renal denervation projected from the global SYMPLICITY registry.

Aims: Renal denervation has been shown to lower blood pressure in sham-controlled trials and represents a device-based treatment option for hypertension. We sought to project clinical event reductions after radiofrequency renal denervation using a novel modelling approach.

Methods And Results: The Global SYMPLICITY Registry is a global, prospective all-comer registry to evaluate safety and efficacy after renal denervation.

Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model.

Background: Sustained blood pressure reductions after radiofrequency (RF) renal denervation (RDN) have been reported to 3 years in patients with uncontrolled hypertension. However, mechanistic data to support procedural durability are lacking. We aimed to quantify the long-term nerve anatomic and functional effects of RF RDN in a preclinical model.

Renal denervation prevents subclinical atrial fibrillation in patients with hypertensive heart disease: Randomized, sham-controlled trial.

Background: Catheter-based renal denervation (RD), in addition to pulmonary vein isolation (PVI), reduces atrial fibrillation (AF) recurrence in hypertensive patients. Whether RD, without additional PVI, can prevent subclinical atrial fibrillation (SAF) in patients with hypertensive heart disease (HHD) is unknown.

Objective: The purpose of this study was to assess the efficacy of RD in preventing SAF in patients with HHD.

Time, Temperature, Power, and Impedance Considerations for Radiofrequency Catheter Renal Denervation.

Radio frequency (RF) based percutaneous catheter renal denervation systems offer an additional clinical tool, along with lifestyle modification and drug therapy, to address the global epidemic of uncontrolled hypertension. The most widely applied RF system has been designed to optimize both procedural and safety and efficacy. Lesion size, shape, and depth result from a complex interaction of device design, anatomy, and tissue electrical conduction properties.

Obstructive Sleep Apnea-Induced Neurogenic Nocturnal Hypertension: A Potential Role of Renal Denervation?

There is a bidirectional, causal relationship between obstructive sleep apnea (OSA) and hypertension. OSA-related hypertension is characterized by high rates of masked hypertension, elevated nighttime blood pressure, a nondipper pattern of nocturnal hypertension, and abnormal blood pressure variability. Hypoxia/hypercapnia-related sympathetic activation is a key pathophysiological mechanism linking the 2 conditions.

Confounding Factors in Renal Denervation Trials: Revisiting Old and Identifying New Challenges in Trial Design of Device Therapies for Hypertension.

Recent randomized sham-controlled trials have demonstrated significant blood pressure reductions following renal denervation (RDN) in patients with hypertension, both in the presence and absence of antihypertensive therapy. These new data encouraged us to revisit previously published insights into potential clinical trial confounding factors that informed the design and conduct of forthcoming trials. Initially identified confounders related to procedural technique, medication variability, and selected patient subgroups have been addressed in contemporary trial design.

Review and meta-analysis of renal artery damage following percutaneous renal denervation with radiofrequency renal artery ablation.

Aims: We aimed to estimate the rate of renal artery adverse events following renal denervation with the most commonly applied radiofrequency catheter system based on a comprehensive review of published reports.

Methods And Results: We reviewed 50 published renal denervation (RDN) trials reporting on procedural safety including 5,769 subjects with 10,249 patient-years of follow-up. Twenty-six patients with renal artery stenosis or dissection (0.

Atrial tachyarrhythmias temporally precede fluid accumulation in implantable device patients.

Background: The complex relationship between heart failure and atrial tachyarrhythmias (AT/atrial fibrillation [AF]) is not well understood. We examined the temporal association between changes in intrathoracic impedance, suggesting thoracic fluid accumulation, and AT/AF occurrence in cardiac resynchronization therapy-defibrillator and implantable cardioverter defibrillator (ICD) patients.

Methods: A retrospective analysis was conducted on stored implantable device data to identify patients with automatic monitoring of daily AT/AF burden and intrathoracic impedance.

Uncovering interim clinical events at the time of clinical encounter by reviewing intrathoracic impedance threshold crossings.

Background: Acute decreases in intrathoracic impedance monitored by implanted devices have been shown to precede heart failure exacerbations, although there is still debate regarding its clinical utility in predicting and preventing future events. However, the usefulness of such information to direct patient encounter and enhance patient recall of relevant preceding clinical events at the point of care has not been carefully examined.

Methods And Results: In this multicenter study, we interviewed 326 patients with heart failure who received an implanted device with intrathoracic impedance-monitoring capabilities both before and after device information was reviewed.

Improved algorithm to detect fluid accumulation via intrathoracic impedance monitoring in heart failure patients with implantable devices.

Background: Intrathoracic impedance fluid monitoring has been shown to predict worsening congestive heart failure (CHF) in patients with implantable devices. We developed and externally validated a modified algorithm to identify worsening heart failure (HF) by using intrathoracic impedance.

Methods And Results: The modified algorithm was developed by using published data from 81 CHF subjects averaging 259 days of follow-up.

Intrathoracic impedance vs daily weight monitoring for predicting worsening heart failure events: results of the Fluid Accumulation Status Trial (FAST).

The relative sensitivity and unexplained detection rate of changes in intrathoracic impedance has not been compared with standard heart failure (HF) monitoring using daily weight changes. The Fluid Accumulation Status Trial (FAST) prospectively followed 156 HF patients with implanted cardioverter-defibrillator or cardiac resynchronization therapy defibrillator devices modified to record daily changes in intrathoracic impedance in a blinded fashion for 537±312 days. Daily impedance changes were used to calculate a fluid index that could be compared with a prespecified threshold.

Human feasibility study of hemodynamic monitoring via continuous intrathoracic impedance monitoring.

The ultimate hemodynamic sensor for an implantable device would provide information about cardiovascular performance including systolic function, diastolic function, preload, and afterload. We examined the potential clinical utility of simultaneous measurement of left ventricular pressure and continuous intrathoracic impedance in a group of 20 patients undergoing acute intravenous ablation for atrial fibrillation. Following baseline measurements of traditional left ventricular (LV) conductance volume (control), LV pressure and conductance measurement were repeated using alternate impedance stimulation and sensing vectors that encompassed combinations of the lung, left ventricle, right ventricle and left atrium, respectively.

Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert.

Background: Acute decreases in intrathoracic impedance monitoring have been shown to precede heart failure hospitalization in a limited population of heart failure patients. We evaluated the relationship between changes in intrathoracic impedance with hospitalizations associated with acute decompensated heart failure (ADHF) in patients with cardiac resynchronization therapy plus defibrillator (CRT-D) devices.

Methods And Results: The study enrolled 326 heart failure patients who had received CRT-D with impedance-monitoring capabilities (InSync Sentry, Medtronic).

Dual-site left ventricular cardiac resynchronization therapy.

Simultaneous stimulation of 2 left ventricular (LV) sites could enhance the effectiveness of cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the acute hemodynamic response to dual-site LV CRT. Two LV pacing leads were successfully implanted in 12 CRT candidates (New York Heart Association classes III to IV, QRS >or=120 ms).