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SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
SAN DIEGO – Pulmonary artery denervation is efficacious for treating combined pre- and postcapillary pulmonary hypertension attributable to left heart failure, based on results of the Chinese PADN-5 trial reported at the Transcatheter Cardiovascular Therapeutics annual meeting.
This ablative treatment has been studied among patients with pulmonary hypertension attributable to other etiologies, but not in randomized fashion among this population, noted lead investigator Shao-Liang Chen, MD, of Nanjing (China) First Hospital, Nanjing Medical University. The treatment is an attractive one, as medications recommended for pulmonary arterial hypertension are not recommended for joint pre- and postcapillary pulmonary hypertension (group II pulmonary hypertension).
In PADN-5, 98 patients were randomized to pulmonary artery denervation or to sham denervation plus open-label sildenafil (Viagra), which at the time of trial initiation was thought to be safe and potentially beneficial.
The trial’s main outcome, 6-minute walk distance at 6 months, improved in both groups, according to data reported at the meeting and simultaneously published in JACC Cardiovascular Interventions. But the improvement was about four times greater in the pulmonary artery denervation group. Secondary efficacy outcomes also favored that group, and the rate of fatal pulmonary embolism did not differ for the two groups.
“The PADN-5 trial demonstrates the benefits of pulmonary artery denervation for patients with combined pre- and postcapillary pulmonary hypertension. Patients with preserved and with reduced ejection fraction equally benefited,” summarized Dr. Chen, who pioneered this procedure about 7 years ago. “There was no sign of any harm of sildenafil in patients with combined pre- and postcapillary pulmonary hypertension.”
Trial critique
“This is a very difficult study to conduct, being able to recruit patients and actually have these procedures done,” commented press conference moderator Ori Ben-Yehuda, MD, professor of clinical medicine and director, coronary care unit, UC San Diego Medical Center.
At the same time, he expressed some reservations about the trial. “Sildenafil in the control group might actually be expected to ... decrease your effect size. Also, particularly in men, perhaps even in women, it might unblind them to which group they are in and undermine your sham design,” he noted. In addition, some hemodynamic changes after pulmonary artery denervation – a decrease in wedge pressure and an increase in ejection fraction – were puzzling.
“We need a lot more data here. There are some issues with this trial in terms of design, and we haven’t even gotten into the issue of whether there were core labs, whether the echoes, the hemodynamics, were read blindly,” Dr. Ben-Yehuda maintained. “This issue of secondary or group II pulmonary hypertension due to left heart failure is one that has been very frustrating in terms of actual PA-specific therapies. So this is an important step further, but it needs confirmation in truly sham-controlled trials that have no potential for unblinding.”
The catheter used in PADN-5 is available in China but has not received clearance in the United States, he pointed out. “There are alternative or competing technologies, one using ultrasound, for example, that has a very similar approach. … We’ll have to see how it ends up [performing].”
Trial details
Patients in the PADN-5 pulmonary artery denervation group underwent ablation only in the periconjunctional area between the distal main trunk and the left ostial branch with a multifunction catheter having premounted electrodes. Those in the control group underwent a sham procedure, with catheter positioning at the target sites and connection to a generator but no ablation, and were given open-label sildenafil. All additionally received standard heart failure medical therapy. (No sildenafil placebo was used in the denervation group.)
Trial results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation, showed that most echocardiographic and hemodynamic measures improved more in the pulmonary artery denervation group.
The greater improvement in 6-minute walk test with denervation versus sham sildenafil at 6 months was evident in a variety of measures: absolute median distance walked (432.5 m vs. 358 m) and mean distance walked (434.6 m vs. 359.4 m), and absolute increase (80 m vs. 17.5 m) and relative increase (21.4% vs. 4.9%) The difference was significant for all measures at P less than .001.
The denervation group had a comparatively greater reduction of pulmonary vascular resistance (29.8% vs. 3.4%; P less than .001) and were less likely to experience clinical worsening (16.7% vs. 40.0%; P = .014).
There was a single fatal pulmonary embolism in each treatment group. Of the seven total deaths, two occurred in the denervation group (one attributable to pump failure, one a sudden death) and five occurred in the sham sildenafil group (all but one attributable to pump failure).
Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
SOURCE: Chen S-J et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.
REPORTING FROM TCT 2018
Key clinical point: Pulmonary artery denervation is efficacious for treating pulmonary hypertension related to heart failure.
Major finding: Improvement in 6-minute walk distance was greater with pulmonary artery denervation than with sham denervation plus sildenafil (21.4% vs. 4.9%; P less than .001).
Study details: PADN-5 is a randomized controlled trial among 98 patients with combined pre- and postcapillary pulmonary hypertension secondary to left heart failure (group II pulmonary hypertension).
Disclosures: Dr. Chen disclosed that he had no relevant conflicts of interest. The trial was sponsored by Nanjing First Hospital, Nanjing Medical University.
Source: Chen S-L et al. TCT 2018. JACC Cardiovasc Interv. 2018 Sep 23.