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). METHODS: This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. RESULTS: A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. CONCLUSIONS: In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

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. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans. RESULTS: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (P=0.003) but not in the RDN group (P=0.44). CONCLUSIONS: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775.

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. For this analysis, change in office systolic blood pressure from baseline was calculated from reported follow-up in the Global SYMPLICITY Registry. Relative risks for death and other cardiovascular events as well as numbers needed to treat for event avoidance were obtained for the respective blood pressure reductions based on previously reported meta-regression analyses for the full cohort and high-risk subgroups including type 2 diabetes, chronic kidney disease, resistant hypertension, and high basal cardiovascular risk. Average baseline office systolic blood pressure and reduction estimates for the full cohort (N = 2651) were 166±25 and -14.8 ± 0.4 mmHg, respectively. Mean reductions in blood pressure ranged from -11.0--21.8 mmHg for the studied high-risk subgroups. Projected relative risks ranged from 0.57 for stroke in the resistant hypertension cohort to 0.92 for death in the diabetes cohort. Significant absolute reductions in major adverse cardiovascular events over 3 years compared with the projected control (8.6 ± 0.7% observed vs. 11.7 ± 0.9% for projected control; P < 0.01) were primarily due to reduced stroke incidence. The robustness of findings was confirmed in sensitivity and scenario analyses. CONCLUSION: Model-based projections suggest radiofrequency renal denervation for patients with uncontrolled hypertension adds considerable clinical benefit across a spectrum of different cohort characteristics.

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. METHODS: Histopathologic analyses were performed on RF-treated renal arteries in a porcine model and untreated control renal arteries. Similar analyses were performed on untreated renal arteries from human cadavers.  Results: In both human and porcine renal arteries, the median number of nerves was lower in the more distal sections (the numbers in the proximal, middle, distal, 1st bifurcation, and 2nd bifurcation sections were 65, 58, 47, 22.5, and 14.7 in humans, respectively, and 39, 26, 29, 16.5, and 9.3 in the porcine models, respectively). Renal nerves were common in the regions between arteries and adjacent veins, but only 3% and 13% of the renal nerves in humans and pigs, respectively, were located behind the renal vein. The semiquantitative score of RF-induced renal arterial nerve necrosis was significantly greater at 7 days than 28 days (0.98 vs 0.75; p=0.01), and injury to surrounding organs was rarely observed. CONCLUSIONS: The distribution of nerve tissue and the relative distribution of extravascular anatomic structures along the renal artery was similar between humans and pigs, which validates the translational value of the normotensive porcine model for RDN.

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. In patients taking at least 3 antihypertensive medications at 36 months (N = 23 RDN group; N = 23 sham group), the 24 h ambulatory SBP as well as morning (7:00-9:00AM) and nighttime (1:00-6:00AM) ambulatory SBP were significantly lower for the RDN group compared to sham control (24 h SBP: -20.2 vs. -10.2, p = 0.0087; morning SBP: -23.9 vs. -8.0 mmHg, p = 0.029; nighttime SBP: -20.8 vs. -7.2 mmHg, p = 0.0011). At 36 months, 24 h SBP was controlled to <130 mmHg in 40% of RDN patients in the morning compared to 6% for the sham group; P = 0.021 and in 80% of the RDN patients at night compared to 39% in the sham group; P = 0.019. Major adverse events through 36 months were rare in both groups, and there were no renal artery re-interventions or vascular complications. Morning and nighttime SBP were significantly lower in patients prescribed at least 3 antihypertensive medications at 36 months in the SPYRAL HTN-ON MED trial for RDN compared with sham control. The results suggest RDN has significant benefit when the risk of cardiovascular events is highest.

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. METHODS: A single-center, randomized, sham-controlled pilot trial, including patients >55 years in sinus rhythm, but with a high risk of developing SAF was conducted. Patients had uncontrolled hypertension despite taking 3 antihypertensive drugs, including a diuretic. The primary endpoint was the first SAF episode lasting ≥6 minutes recorded via an implantable cardiac monitor scanned every 6 months for 24 months. A blinded independent monitoring committee assessed electrocardiographic rhythm recordings. Change in SAF burden (SAFB), and office and 24-hour ambulatory blood pressure (BP) at 6-month follow-up were secondary endpoints. RESULTS: Eighty patients were randomly assigned to RD (n = 42) or sham groups (n = 38). After 24 months of follow-up, SAF occurred in 8 RD patients (19%) and 15 sham patients (39.5%) (hazard ratio 0.40; 95% confidence interval 0.17-0.96; P = .031). Median [interquartile range] SAFB was low in both groups but was significantly lower in the RD vs sham group (0% [0-0] vs 0% [0-0.3]; P = .043). Fast AF (>100 bpm) occurred less frequently in the RD than sham group (2% vs 26%; P = .002). After adjusting for baseline values, there were no significant differences in office or 24-hour BP changes between treatment groups. CONCLUSION: RD reduced incident SAF events, SAFB, and fast AF in patients with HHD. The observed effects may occur independent of BP lowering.

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. METHODS: Bilateral RF RDN was performed in 20 normotensive swine. Renal tissue samples were obtained in the RDN-treated groups at 7 ( n  = 6), 28 ( n  = 6), and 180 days ( n  = 8) postprocedure for quantification of cortical norepinephrine (NE) levels and renal cortical axon density. Tissue fibrosis, necrosis and downstream nerve fiber atrophy (axonal loss) were also scored for each sample. Three additional untreated groups ( n  = 6, n  = 6 and n  = 8, respectively) served as control. RESULTS: Pathologic nerve changes were characterized by necrosis in the ablated region at 7 days that partially resolved by 28 days and fully resolved at 180 days. Axonal loss was apparent within and downstream to the ablation regions and was evident at 7, 28 and 180 days in the main vessel and branch vessels. Consequently, renal cortical axon density and corresponding cortical NE levels were significantly reduced at 7 days in the RDN vs. control group and remained suppressed at 180 days. CONCLUSIONS: Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.

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. Power control algorithms must be carefully designed, incorporating feedback to maximize nerve destruction while minimizing collateral damage. Physical and numerical modelling as well as analysis of sensor feedback provide insight into design performance that cannot be derived from clinical trials. This review is focused on key design and performance aspects of the most widely applied renal denervation system meant to optimize safety and efficacy of the procedure.

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. Intermittent hypoxia also stimulates the renin-angiotensin-aldosterone system to promote hypertension development. The negative and additive cardiovascular effects of OSA and hypertension highlight the importance of effectively managing these conditions, especially when they coexist in the same patient. Continuous positive airway pressure is the gold standard therapy for OSA but its effects on blood pressure are relatively modest. Furthermore, this treatment did not reduce the cardiovascular event rate in nonsleepy patients with OSA in randomized controlled trials. Antihypertensive agents targeting sympathetic pathways or the renin-angiotensin-aldosterone system have theoretical potential in comorbid hypertension and OSA, but current evidence is limited and combination strategies are often required in drug resistant or refractory patients. The key role of sympathetic nervous system activation in the development of hypertension in OSA suggests potential for catheter-based renal sympathetic denervation. Although long-term, randomized controlled trials are needed, available data indicate sustained and relevant reductions in blood pressure in patients with hypertension and OSA after renal denervation, with the potential to also improve respiratory parameters. The combination of lifestyle interventions, optimal pharmacological therapy, continuous positive airway pressure therapy, and perhaps also renal denervation might improve cardiovascular risk in patients with OSA.

Improved blood pressure control via a novel chronic disease management model of care in sub-Saharan Africa: Real-world program implementation results.

A chronic disease management model of care (Empower Health) was launched in rural and urban areas of Ghana and Kenya in 2018. The goal was to improve disease awareness, reduce the burden of disease, and improve the clinical effectiveness and efficiency of managing hypertension. Leveraging the model, clinicians provide patients with tailored management plans. Patients accessed regular blood pressure checks at home, at the clinic, or at community-partner locations where they received real-time feedback. On the mobile application, clinicians viewed patient data, provided direct patient feedback, and wrote electronic prescriptions accessible through participating pharmacies. To date, 1266 patients had been enrolled in the "real-world" implementation cohort and followed for an average of 351 ± 133 days across 5 facilities. Average baseline systolic blood pressure (SBP) was 145 ± 21 mmHg in the overall cohort and 159 ± 16 mmHg in the subgroup with uncontrolled hypertension (n = 743) as defined by baseline SBP ≥ 140 mmHg. SBP decreased significantly through 12 months in both the overall cohort (-9.4 mmHg, p < .001) and in the uncontrolled subgroup (-17.6 mmHg, p < .001). The proportion patients with controlled pressure increased from 46% at baseline to 77% at 12 months (p < .001). In summary, a new chronic disease management model of care improved and sustained blood pressure control to 12 months, especially in those with elevated blood pressure at enrollment.

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. Regarding procedural method and technology, blood pressure reductions may be improved by ensuring circumferential lesion creation in the distal renal arteries and branch vessels. Safety of the RDN procedure has been demonstrated in multiple independent meta-analyses including thousands of treated patients with low reported rates of renal vessel complications and maintenance of renal function. However, a newer generation of RDN trials has also introduced insights related to medication adherence, patient selection, and the definition of treatment response. Evolving evidence indicates that RDN therapy may be considered in higher risk populations of uncontrolled hypertension regardless of ethnicity and in patients expressing a strong preference for a nondrug therapy option. Despite advances in procedural technique and clinical trial conduct, inconsistent antihypertensive-drug adherence behavior remains perhaps the most critical clinical trial design issue for device-based hypertension therapies. As the balance in clinical equipoise increasingly favors RDN, justification of sham-controlled trial designs will be revisited, and novel study designs may be required to evaluate the safety and efficacy of novel devices and procedures intended to address the escalating prevalence of poorly controlled hypertension.

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 (0.45%) were identified of whom 24 (0.41%) required renal artery stenting. The primary meta-analysis of all reports indicated a 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.12 to 0.29% per year). Additional sensitivity analyses yielded consistent pooled estimates (range: 0.17 to 0.42% per year). Median time from RDN procedure to all renal intervention was 5.5 months (range: 0 to 33 months); 79% of all events occurred within one year of the procedure. A separate review of 14 clinical trials reporting on prospective follow-up imaging using either magnetic resonance imaging, computed tomography or angiography following RDN in 511 total subjects identified just 1 new significant stenosis (0.20%) after a median of 11 months post procedure (one to 36 months). CONCLUSIONS: Renal artery reintervention following renal denervation with the most commonly applied RF renal denervation system (Symplicity) is rare. Most events were identified within one year.

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. Daily population trends in AT/AF burden before and after a fluid index threshold crossing (FIC) were determined. RESULTS: A total of 73,018 patients (68 ± 12 years, 51% ICD, 75% male) were evaluated over 18.6 ± 11.5 months. Kaplan-Meier analysis indicated a significantly higher probability of FIC events in the first month following the onset of persistent AT/AF when compared to a matched group without persistent AT/AF (hazard ratio [HR] 1.65, 95% confidence interval [CI] [1.58, 1.72], P < 0.001). Conversely, patients were significantly more likely to experience an episode of persistent AF in the first month after the FIC event (HR 1.32, 95% CI [1.08, 1.63], P = 0.008). The probability of a fluid index crossing within 30 days of the onset of persistent AT/AF was significantly lower in a subgroup of patients with adequate rate control (35.8% [34.3-37.4%] vs 42.0% [39.6-44.6%]; HR 1.24 [1.13-1.36]). CONCLUSION: Thoracic fluid accumulation, as indicated by decreasing intrathoracic impedance, was more likely to occur immediately after the onset of persistent AT/AF, especially in the presence of inadequate rate control. Likewise, the onset of persistent AT/AF was more likely following a decrease in 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. We compared the self-reported clinically relevant events (including heart failure hospitalizations, signs and symptoms of worsening heart failure, changes in diuretic therapy, or other fluid-related events) obtained before and after device interrogation, and then examined the relationship between such events with impedance trends documented by the devices. Over 333 ± 96 days of device monitoring, 215 of 326 patients experienced 590 intrathoracic impedance fluid index threshold-crossing events at the nominal threshold value (60 Ω-d). Review of device-derived information led to the discovery of 221 (37%) previously unreported clinically relevant events in 138 subjects. This included 60 subjects not previously identified as having had clinically relevant events (or 35% of the 171 subjects who did not report events). CONCLUSIONS: Our data demonstrated that reviewing device-derived intrathoracic impedance trends at the time of clinical encounter may help uncover self-reporting of potential clinically relevant events.

Progression of new onset to established persistent atrial fibrillation: an implantable device-based analysis with implications for clinical classification of persistent atrial fibrillation.

INTRODUCTION: The temporal patterns of onset of persistent atrial fibrillation (AF) recurrences leading to established persistent AF is currently unknown. METHODS: Three hundred thirty patients with a history of paroxysmal AF and bradycardia (mean age, 70 ± 10 years; 61% male) with implanted pacemakers that automatically recorded the cumulative daily atrial tachyarrhythmia (AT) burden were included in the analysis. Persistent AF was defined as device data showing ≥7 consecutive days with ≥23 h of AT. We analyzed the pattern and duration of persistent AF recurrences and time to each persistent AF episode recurrence. RESULTS: Seventy-eight patients (24%) developed their first persistent AT/AF after 147 ± 149 days. Follow up ranged from 14 to 499 days. Median AF burden in the week prior to persistent AF was 3.5 h/day. Fifty-four patients (16%) had a minimum of 180 days follow up after initial detection of persistent AF. Three of 54 patients (6%) immediately developed established AF; 32 of 51 patients (63%) returned to sinus rhythm but then had a second persistent AF event. These 32 patients had a minimum of 90 days follow up and 25 of these 32 patients (78 %) had a third persistent AF event. Time to recurrence analysis showed progressive abbreviation in persistent AF onset. The median durations of the first, second, and third persistent AF events were 16, 13, and 17 days, respectively. CONCLUSIONS: (1) The time to first, second, and third persistent AF recurrences progressively decreases with a high likelihood of established persistent AF within 9 months of onset. (2) These data support intermittent but frequent AF monitoring for the detection of persistent AF recurrences to assess the efficacy of rhythm control interventions.

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. Device-measured daily impedance was input to both the existing and the modified intrathoracic impedance fluid monitoring algorithms to determine a reference impedance and a fluid index (FI). Separate validation sets included 326 cardiac resynchronization therapy device (CRT-D) patients with an average 333 days of follow-up (group 1) and 104 CRT-D/implantable cardioverter/defibrillator (ICD) patients followed for an average of 520 days (group 2). Clinicians and patients in group 2 were blinded to impedance and FI data. HF events included adjudicated HF hospitalizations or emergency room visits. Sensitivity was defined as the percentage of HF events preceded by FI exceeding the predefined threshold (60 Ω-d) within the last 2 weeks. Unexplained detections were FI threshold crossing events not followed by a HF event within 2 weeks. The modified algorithm significantly decreased unexplained detections by 30% (P = .01; GEE) in the development set, 30% (P < .001) in the group 1 validation set, and 43% (P < .001) in group 2. Sensitivity did not change significantly in any group. Simulated monthly review of FI threshold crossings identified subjects at significantly greater risk of worsening HF within the next 30 days. CONCLUSIONS: A modified intrathoracic impedance based fluid detection algorithm lowered the number of unexplained FI threshold crossings and identified patients at significantly increased immediate risk of worsening HF.

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. True positives were defined as adjudicated episodes of worsening HF occurring within 30 days of a fluid index above threshold or an acute weight gain. Unexplained detections were defined as threshold crossings or acute weight gains not associated with worsening HF. Impedance measurements were performed on >99% of follow-up days, compared with only 76% of days for weight measurements. Sixty-five HF events occurred during follow-up (0.32/patient-year). Forty HF events were detected by impedance but not weight, whereas 5 were detected by weight but not impedance. Sensitivity was greater (76% vs 23%; P<.0001) and unexplained detection rate was lower (1.9 vs 4.3/patient-year; P<.0001) for intrathoracic impedance monitoring at the threshold of 60Ω days compared with acute weight increases of 3 lbs in 1 day or 5 lbs in 3 days and also over a wide range of fluid index and weight thresholds. The sensitivity and unexplained detection rate of intrathoracic impedance monitoring was superior to that seen for acute weight changes. Intrathoracic impedance monitoring represents a useful adjunctive clinical tool for managing HF in patients with implanted devices.