Ventricular Tachycardia
Conditions
Keywords
Tachycardia, Renal Sympathetic Denervation, Catheter Ablation, Cardioverter-Defibrillator
Brief summary
Despite significant advances in the management of ventricular arrhythmias through the use of ICD therapy, AADs, and catheter-based ablation strategies, considerable challenges remain. The optimal method for the prevention of recurrent VT following catheter ablation remains unclear. RSDN may be an effective tool for preventing ventricular arrhythmias, and associated ICD therapies, by reducing central sympathetic tone, catecholamine levels, and the renin-angiotensin- aldosterone system and promoting ventricular remodeling. Although RSDN has been shown to reduce the recurrence of VT in a case report of 2 patients suffering from electrical storm, to date no large prospective randomized study has evaluated the impact of RSDN in the prevention of recurrent VT in patients following catheter ablation of VT with ischemic or non-ischemic ventricular dysfunction. This study will specifically evaluate the safety and efficacy of adjunctive RSDN in the prevention of ICD therapy in patients with ischemic or non-ischemic ventricular dysfunction who are to receive a catheter-based VT ablation.
Detailed description
The goal of this trial is to test the impact of catheter-based renal sympathetic denervation (RSDN) as an adjunctive treatment for patients with either ischemic or non-ischemic cardiomyopathy undergoing catheter ablation of ventricular tachycardia (VT). The proposed study is a prospective, multicenter, randomized control trial. Patients undergoing VT ablation will be randomized to either VT ablation alone or VT ablation + RSDN.
Interventions
* The ablation catheter is placed within a long vascular sheath and advanced into the renal artery. The sheath is advanced over the catheter to engage the renal artery ostium and allow for contrast injection and visualization of the vessel during catheter manipulation. * After completion of the measurement, no more than six radiofrequency ablation lesions separated both longitudinally and rotationally (a spiral pattern, see figure) will be placed per renal artery. The power will be started at 10 W and titrated to a maximum 20 W, as deemed appropriate by the impedance drop (goal 10% drop). Each lesion should be between 30-120 seconds in duration (no more than 120 seconds per lesion).
DEVICEVT ablation alone
Placebo arm will receive standard VT ablation using current techniques
Sponsors
Vivek Reddy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age * Structural heart disease (post-MI, dilated cardiomyopathy, sarcoid myopathy, hypertrophic cardiomyopathy, chagas-related cardiomyopathy, etc.) * Planned for catheter-based ablation of VT * All patients will have an existing ICD * Accessibility of renal vasculature (determined by renal angiography) * Ability to understand the requirements of the study * Willingness to adhere to study restrictions and comply with all post- procedural follow-up requirements
Exclusion criteria
* MI or CVA within 30 days * Coronary Artery Bypass Graft (CABG) within 30 days of this procedure * Known renovascular abnormalities that would preclude RSDN (eg, renal artery stenosis) * GFR \<30 ml/min (unless receiving dialysis) * Life expectancy \<1 year for any medical condition * Any condition resulting in a contraindication to anticoagulation (e.g. GI bleeding) * Inability to give informed consent * Known pregnancy or positive -HCG within 7 days of procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From First Event Requiring ICD Therapy | 24 months | Probability of freedom from first event requiring ICD therapy at 12 months and at 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Inappropriate ICD Therapy | at 24 months | Number of inappropriate ICD therapy including both appropriate and inappropriate shocks |
| All ICD Therapies (Appropriate + Inappropriate) | 24 months | cumulative ICD therapies including both appropriate and inappropriate shocks |
| Number of Participants With Mortality, ICD Storm and Incessant VT | 24 months | Number of Participants with a composite of Mortality, ICD storm, and Incessant VT |
| Number of Participants With Hospitalizations for Cardiovascular Causes | 24 months | — |
| Number of Episodes of Total VT Burden | at 24 months | Total VT burden (Number of episodes) |
| Number of Participants With All-Cause Mortality | 24 months | — |
| Number of Participants With Occurrences of ICD Storm | 24 months | The occurrence of ICD storm, defined as ≥3 appropriate shock therapies within 24 hours. |
| Change in Brain Natriuretic Peptide (BNP) | at baseline and at 12 months | Differences in blood hormone measurements as measured by BNP as compared on 12 months to baseline. |
| Number of Appropriate ICD Shocks for Ventricular Arrhythmia | at 24 months | An Appropriate ICD therapy is defined as anti-tachycardia pacing (ATP) or shock therapy for ventricular tachycardia or fibrillation. |
| Change in LV Size | baseline and 12 months | LV size measured by trans-thoracic echocardiography, as compared at 12 months to baseline |
| Number of Procedure-related Adverse Events | 24 months | Procedure related adverse events including, but not limited to hematomas, pseudoaneurysms, renal artery stenosis, renal impairment, thromboembolic events, stroke, pericardial bleeding including tamponade and myocardial infarction. |
| Changes in Mean Arterial Pressure | baseline and 24 months | Change in mean arterial pressure |
| Number of Participants With Orthostatic Hypertension | 24 months | Number of participants with other individual complication rates specifically orthostatic hypertension |
| Number of Participants With Other Complications | at 24 months | Other individual complication rates including, but not limited to MI and death |
| Number of Occurrences of Major Complication Rate | 30 days | 30-day Major Complication Rate defined as death, stroke, MI or any other serious adverse events related to the treatment or procedure within the first 30 days or through hospital discharge (whichever is longer) |
| Procedure Time | during procedure | Renal Denervation Procedure time |
| Differences in BUN/Creatinine Measurements | baseline and 12 months | Differences in BUN/creatinine measurements compared at 12 months to baseline. |
Countries
Czechia, United States
Participant flow
Recruitment details
21 participants received ID numbers because they were consented. 3 patients were screen failures due to accessibility of renal vasculature and Investigator discretion. 1 patient was a non-randomized roll- in where data was not collected.
Participants by arm
| Arm | Count |
|---|---|
| VT Ablation Alone VT ablation alone: Placebo arm will receive standard VT ablation using current techniques | 8 |
| Renal Sympathetic Denervation Catheter-based Renal Sympathetic Denervation Ablation Arm
Renal sympathetic denervation: • The ablation catheter is placed within a long vascular sheath and advanced into the renal artery. The sheath is advanced over the catheter to engage the renal artery ostium and allow for contrast injection and visualization of the vessel during catheter manipulation.
• After completion of the measurement, no more than six radiofrequency ablation lesions separated both longitudinally and rotationally (a spiral pattern, see figure) will be placed per renal artery. The power will be started at 10 W and titrated to a maximum 20 W, as deemed appropriate by the impedance drop (goal 10% drop). Each lesion should be between 30-120 seconds in duration (no more than 120 seconds per lesion). | 9 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Total Artificial Heart Implant | 0 | 1 |
Baseline characteristics
| Characteristic | Renal Sympathetic Denervation | Total | VT Ablation Alone |
|---|---|---|---|
| Age, Continuous | 56.78 years STANDARD_DEVIATION 9.43 | 58.88 years STANDARD_DEVIATION 9.12 | 61.5 years STANDARD_DEVIATION 8.73 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 13 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 5 / 9 | 3 / 8 |
| serious Total, serious adverse events | 3 / 9 | 2 / 8 |
Outcome results
Primary
Freedom From First Event Requiring ICD Therapy
Probability of freedom from first event requiring ICD therapy at 12 months and at 24 months
Time frame: 24 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Renal Sympathetic Denervation | Freedom From First Event Requiring ICD Therapy | 12 months | 62.5 probability of freedom |
| Renal Sympathetic Denervation | Freedom From First Event Requiring ICD Therapy | 24 months | 62.5 probability of freedom |
| VT Ablation Alone | Freedom From First Event Requiring ICD Therapy | 12 months | 50 probability of freedom |
| VT Ablation Alone | Freedom From First Event Requiring ICD Therapy | 24 months | 37.5 probability of freedom |
Secondary
All ICD Therapies (Appropriate + Inappropriate)
cumulative ICD therapies including both appropriate and inappropriate shocks
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | All ICD Therapies (Appropriate + Inappropriate) | 32 occurrences |
| VT Ablation Alone | All ICD Therapies (Appropriate + Inappropriate) | 32 occurrences |
Secondary
Change in Brain Natriuretic Peptide (BNP)
Differences in blood hormone measurements as measured by BNP as compared on 12 months to baseline.
Time frame: at baseline and at 12 months
Population: results only for those participants who have both timepoint data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Sympathetic Denervation | Change in Brain Natriuretic Peptide (BNP) | -12.33 mg/dL | Standard Deviation 46.6 |
| VT Ablation Alone | Change in Brain Natriuretic Peptide (BNP) | -2.5 mg/dL | Standard Deviation 24.75 |
Secondary
Change in LV Size
LV size measured by trans-thoracic echocardiography, as compared at 12 months to baseline
Time frame: baseline and 12 months
Population: Results only available for participants with data for both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Sympathetic Denervation | Change in LV Size | -.125 cm | Standard Deviation 0.59 |
| VT Ablation Alone | Change in LV Size | -1.4 cm | — |
Secondary
Changes in Mean Arterial Pressure
Change in mean arterial pressure
Time frame: baseline and 24 months
Population: Results only available for participants with data for both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Sympathetic Denervation | Changes in Mean Arterial Pressure | 3.33 mmHg | Standard Deviation 8.41 |
| VT Ablation Alone | Changes in Mean Arterial Pressure | 13.77 mmHg | Standard Deviation 18.75 |
Secondary
Differences in BUN/Creatinine Measurements
Differences in BUN/creatinine measurements compared at 12 months to baseline.
Time frame: baseline and 12 months
Population: Results only available for participants with data for both timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation | Differences in BUN/Creatinine Measurements | BUN | -4 mg/dL | Standard Deviation 4.84 |
| Renal Sympathetic Denervation | Differences in BUN/Creatinine Measurements | Creatinine | 0.095 mg/dL | Standard Deviation 0.24 |
| VT Ablation Alone | Differences in BUN/Creatinine Measurements | BUN | 1.67 mg/dL | Standard Deviation 5.68 |
| VT Ablation Alone | Differences in BUN/Creatinine Measurements | Creatinine | .04 mg/dL | Standard Deviation 0.03 |
Secondary
Number of Appropriate ICD Shocks for Ventricular Arrhythmia
An Appropriate ICD therapy is defined as anti-tachycardia pacing (ATP) or shock therapy for ventricular tachycardia or fibrillation.
Time frame: at 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Appropriate ICD Shocks for Ventricular Arrhythmia | 7 occurrences |
| VT Ablation Alone | Number of Appropriate ICD Shocks for Ventricular Arrhythmia | 12 occurrences |
Secondary
Number of Episodes of Total VT Burden
Total VT burden (Number of episodes)
Time frame: at 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Episodes of Total VT Burden | 20 episodes |
| VT Ablation Alone | Number of Episodes of Total VT Burden | 12 episodes |
Secondary
Number of Inappropriate ICD Therapy
Number of inappropriate ICD therapy including both appropriate and inappropriate shocks
Time frame: at 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Inappropriate ICD Therapy | 5 occurrences |
| VT Ablation Alone | Number of Inappropriate ICD Therapy | 7 occurrences |
Secondary
Number of Occurrences of Major Complication Rate
30-day Major Complication Rate defined as death, stroke, MI or any other serious adverse events related to the treatment or procedure within the first 30 days or through hospital discharge (whichever is longer)
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Occurrences of Major Complication Rate | 2 occurrences |
| VT Ablation Alone | Number of Occurrences of Major Complication Rate | 3 occurrences |
Secondary
Number of Participants With All-Cause Mortality
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With All-Cause Mortality | 0 Participants |
| VT Ablation Alone | Number of Participants With All-Cause Mortality | 0 Participants |
Secondary
Number of Participants With Hospitalizations for Cardiovascular Causes
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With Hospitalizations for Cardiovascular Causes | 3 Participants |
| VT Ablation Alone | Number of Participants With Hospitalizations for Cardiovascular Causes | 1 Participants |
Secondary
Number of Participants With Mortality, ICD Storm and Incessant VT
Number of Participants with a composite of Mortality, ICD storm, and Incessant VT
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With Mortality, ICD Storm and Incessant VT | 1 Participants |
| VT Ablation Alone | Number of Participants With Mortality, ICD Storm and Incessant VT | 3 Participants |
Secondary
Number of Participants With Occurrences of ICD Storm
The occurrence of ICD storm, defined as ≥3 appropriate shock therapies within 24 hours.
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With Occurrences of ICD Storm | 1 Participants |
| VT Ablation Alone | Number of Participants With Occurrences of ICD Storm | 3 Participants |
Secondary
Number of Participants With Orthostatic Hypertension
Number of participants with other individual complication rates specifically orthostatic hypertension
Time frame: 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With Orthostatic Hypertension | 0 Participants |
| VT Ablation Alone | Number of Participants With Orthostatic Hypertension | 0 Participants |
Secondary
Number of Participants With Other Complications
Other individual complication rates including, but not limited to MI and death
Time frame: at 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Participants With Other Complications | 1 Participants |
| VT Ablation Alone | Number of Participants With Other Complications | 2 Participants |
Secondary
Number of Procedure-related Adverse Events
Procedure related adverse events including, but not limited to hematomas, pseudoaneurysms, renal artery stenosis, renal impairment, thromboembolic events, stroke, pericardial bleeding including tamponade and myocardial infarction.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation | Number of Procedure-related Adverse Events | 3 events |
| VT Ablation Alone | Number of Procedure-related Adverse Events | 3 events |
Secondary
Procedure Time
Renal Denervation Procedure time
Time frame: during procedure
Population: Results only for those participants who underwent renal sympathetic denervation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VT Ablation Alone | Procedure Time | 27.83 minutes | Standard Deviation 8.8 |