阅读说明：本技术 用于通过改善患者的射血分数来治疗心力衰竭的方法 (Method for treating heart failure by the ejection fraction for improving patient ) 是由 欧尔·沙比泰 达利特·沙夫 于 2018-03-20 设计创作，主要内容包括：一种用于改善有此需要的患者的射血分数的方法,所述方法包括：将肺动脉操纵装置定位在所述患者的肺脉管系统内的目标血管中；和使用所述肺动脉操纵装置削弱至少一个交感神经、神经纤维或神经元的活动以将所述目标血管去神经支配,从而改善所述患者的射血分数。(A method of for improving the ejection fraction of patient with this need, which comprises be located in pulmonary artery manipulation device in the target blood in the pulmonary vasculature of the patient；With use the pulmonary artery manipulation device to weaken the activity of at least one sympathetic nerve, nerve fibre or neuron with by the target blood denervation, so as to improve the ejection fraction of the patient.)

1. a kind of for improving the method for the ejection fraction of patient with this need, which comprises

Pulmonary artery manipulation device is located in the target blood in the pulmonary vasculature of the patient；With

Weaken the activity of at least one sympathetic nerve, nerve fibre or neuron using the pulmonary artery manipulation device with will be described Target blood denervation, so as to improve the ejection fraction of the patient.

2. according to the method described in claim 1, wherein the ejection fraction is left ventricular ejection fraction.

3. according to the method described in claim 1, wherein the ejection fraction is right ventricular ejection fraction.

4. according to the method in any one of claims 1 to 3, wherein the therapeutic device includes energy transform device, described Energy transform device transmitting is selected from the energy of group being made up of: monopolar radio frequency, bipolar radio frequency, ultrasound, microwave, light, heat, cold Radiation, phototherapy, magnetic, electricity, electromagnetism, cold treatment, plasma, machinery, chemistry, dynamics, gesture, core, elasticity and hydrodynamic energy, It and the use of the therapeutic device include wherein the emitted energy from conduit.

5. method according to claim 1 to 4, wherein the therapeutic device includes ultrasound transmission apparatus.

6. according to the method described in claim 5, wherein emitting supersonic beam with the frequency of 1-20MHz.

7. according to the method described in claim 6, wherein emitting supersonic beam with the frequency of 8-12MHz.

8. method according to any one of claim 1 to 7, wherein the ejection fraction for improving the patient includes reducing institute State the pulmonary vascular resistance (PVR) at least one artery of pulmonary vasculature.

9. method according to any one of claim 1 to 8, wherein the patient has the lung of at least three wood's unit Vascular resistence (PVR).

10. according to the method described in claim 9, wherein when reducing pulmonary capillary wedge pressure (PCWP) of the patient, institute PVR holding is stated to be basically unchanged.

11. method according to any one of claim 1 to 10, wherein when with diuretics, vasodilator, anti-hypertension When drug, oxygen or any combination thereof treat the patient, the PVR holding is basically unchanged.

12. method according to any one of claim 1 to 11, wherein the target blood denervation is made to include drop The tension of smooth muscle in the wall of the low target blood.

13. method according to any one of claim 1 to 12, wherein weakening at least one sympathetic nerve, nerve fibre Or the activity of neuron includes emitting supersonic beam from the pulmonary artery manipulation device.

14. according to the method for claim 13, wherein the supersonic beam is unfocused supersonic beam.

15. according to the method described in claim 1, further including indicating one or more secondary works on the specification of the method With.

16. according to the method for claim 15, wherein one or more side effects are selected from the group being made up of: the heart Restrain disorder, bradycardia；Blood clot formation, embolism, ischaemic, ischaemic event, myocardial infarction, stroke, hemoptysis, blood Swollen, contusion, bleeding, vascular complication, arteriospasm, arteriarctia, artery removing, perforation, lung perforation, false aneurysm, AV Fistula；Allergic reaction, decreased renal function, pain, infection, Nausea and vomiting, fever, death, cardiopulmonary all standing, anxiolytic, anodyne Habituation is side effect relevant to anodyne used in surgical procedure, related with vasospasm medicine used in surgical procedure Side effect, with infection, toxicity, unfavorable hematology, bleeding, hemoptysis, Pyrogenicity, vascular wall or other body structures damage, Pulmonary stenosis, neurotrosis, spasm, Aneurysmformation, aneurysm rupture, topography damage, plexus cardiacus damage Wound, esophageal injury, tracheal injury, injury of lungs, vagus nerve injury, bradycardia, tachycardia, part paralysis vocal cord, hemoptysis, The relevant side effect of decline in pulmonary function, hypertension, hypoperfusion or any combination thereof.

Technical field

Improve the field of the ejection fraction of patient present disclosure generally relates to pulmonary artery denervation.

Background technique

Ejection fraction refers to the percentage for the blood that each heartbeat is pumped out from full ventricle.Left ventricular ejection fraction is Measurement to the efficiency for being pumped into body circulation, and right ventricular ejection fraction is the measurement to the efficiency for being pumped into pulmonary circulation.Left ventricle is The main pump chamber of heart, the blood that will be enriched in oxygen are pumped into the rest part of body by aorta ascendens (upward), therefore Ejection fraction is usually measured in left ventricle (LV).Its by the way that stroke output is calculated divided by end-diastolic volume, and It is the intrinsic measurement of heart pumping efficiency.The busy heart beated but many blood cannot successfully be discharged considered to be in heart failure It exhausts.

Ejection fraction reduction may there are many reasons, including heart damage caused by cardiomyopathy, heart attack, heart valve Malfunction, long-term uncontrolled hypertension, high lung ventricle resistance, low dilatancy of artery etc..

Ejection fraction is usually measured by echocardiogram, and is used as the general measurement of human heart function.It is other more seldom The method seen includes heart catheterization, MRI, CT and kernel method, such as PET, SPECT and MUGA, wherein micro is put Penetrating property substance (such as thallium) injects in blood flow, and when it flows through heart and lung with putting in special camera detection blood Penetrating property substance.

The normal ejection fraction for showing good ventricular contractility is 50% to 75%.Ejection fraction reduction (is less than 50%) reduced heart pumping efficiency is indicated, in this case, enough blood can not be pumped into the other of body by heart Remaining part position, thus it is unable to satisfy the demand of body.Ejection fraction reduce patient often suffer from be short of breath, can not move, under Limb swelling, fatigue and weakness, amentia and cardiac arrhythmia.35% or lower ejection fraction show heart failure, stethemia, The risk of cardiomegaly or heart enlargement and liver or renal insufficiency increases.

Summary of the invention

In some embodiments of present disclosure, it is related in terms of present disclosure for improving patient with this need Ejection fraction method.

Appropriate reduction can be improved by so-called lifestyle change (including low salt diet, fluid management and movement) Ejection fraction.But such lifestyle change is often inadequate.Some drugs can help to mitigate the negative of heart Load increases blood flow, expands blood vessel or eliminates moisture extra in vivo, all these all to can help to treatment grazing shot blood system Number.Common prescription medicine includes: positive inotropic medicament (Inotrope) (such as digoxin), angiotensin-ii receptor retarding agent And beta-blocker.But some patients do not respond to these drugs, and as an alternative by defibrillator implantation.Cause This, it is still desirable to is for improving the invasive methods of the ejection fraction of patient.

Advantageously, method described herein is by making pulmonary vasculature denervation and adjusting or reduce sympathetic nerve Power can improve the ejection fraction of patient.In terms of it, the method, which is related to for artery manipulation device being located in, for example penetrates blood system Target blood in the pulmonary vasculature of the reduceds patients of number it is interior or near, and using artery manipulation device weaken at least one friendship The activity of sense nerve, nerve fibre or neuron.The weakening of nerve, nerve fibre or neuron leads to the denervation of target blood It dominates, and therefore leads to the improvement of ejection fraction.

Many treats most conventional with the patient that ejection fraction reduces resistant.Method disclosed herein is advantageously For usually not actual therapeutic choice, the available patient reduced with ejection fraction provides treatment.Therefore, this method is to work as It is preceding not treat available patient effectively and provide effective treatment solution.

According to some embodiments, provide it is a kind of for improving the method for the ejection fraction of patient with this need, it is described Method includes: in the target blood that pulmonary artery manipulation device is located in the pulmonary vasculature of patient；With use pulmonary artery to grasp Vertical device weakens the activity of at least one sympathetic nerve, nerve fibre or neuron with by target blood denervation, thus Improve the ejection fraction of patient.

According to some embodiments, ejection fraction is left ventricular ejection fraction.

According to some embodiments, ejection fraction is right ventricular ejection fraction.

According to some embodiments, therapeutic device includes energy transform device, energy transform device transmitting selected from by with The energy of the group of lower composition: monopolar radio frequency, bipolar radio frequency, ultrasound, microwave, light, heat, cold emission, phototherapy, magnetic, electricity, electromagnetism, cold Treatment, plasma, machinery, chemistry, dynamics, gesture, core, elasticity and hydrodynamic energy, and wherein filled using the treatment It sets including the emitted energy from conduit.

According to some embodiments, therapeutic device includes ultrasound transmission apparatus.According to some embodiments, with the frequency of 1-20MHz Rate emits supersonic beam.According to some embodiments, supersonic beam is emitted with the frequency of 8-12MHz.

According to some embodiments, the ejection fraction for improving patient includes reducing pulmonary vascular resistance (PVR).According to some implementations Example, patient have the pulmonary vascular resistance (PVR) of at least three wood's unit.

According to some embodiments, as pulmonary capillary wedge pressure (the pulmonary capillary wedge for reducing patient Pressure, PCWP) when, PVR holding is basically unchanged.

According to some embodiments, controlled when with diuretics, vasodilator, drug for hypertension, oxygen or any combination thereof When treating patient, PVR holding is basically unchanged.

According to some embodiments, making target blood denervation includes reducing of the smooth muscle in target vessel wall Power.

According to some embodiments, it includes dynamic from lung for weakening the activity of at least one sympathetic nerve, nerve fibre or neuron Arteries and veins manipulation device emits supersonic beam.According to some embodiments, supersonic beam is unfocused supersonic beam.

According to some embodiments, the ejection fraction for improving patient includes improving the Pulmonary Vascular dilatancy of patient.

According to some embodiments, the ejection fraction for improving patient includes improving the pulmonaly artery compliance of patient.

According to some embodiments, the ejection fraction for improving patient includes reducing the Pulmonary Vascular rigidity of patient.

According to some embodiments, the ejection fraction for improving patient includes reducing the Pulmonary Vascular systolic pressure of patient.

According to some embodiments, the ejection fraction for improving patient includes the right atrial pressure for reducing patient.According to some realities Example is applied, the ejection fraction for improving patient includes the cardiac output for increasing patient.

According to some embodiments, the ejection fraction for improving patient includes the cardiac index (cardiac for increasing patient index).According to some embodiments, the ejection fraction for improving patient includes the right atrial pressure for increasing patient.According to some implementations Example, the ejection fraction for improving patient lead to the improvement of quality of life (quality of life, QoL) parameter.According to some implementations Example, denervation treatment disclosed herein can improve the compliance of proximal end pulmonary artery, after this can then reduce right ventricle Load.

According to some embodiments, the method also includes one or more side effects are indicated on the specification of method.

According to some embodiments, one or more side effects are selected from the group being made up of: arrhythmia, bradycardia； Blood clot formation, embolism, ischaemic, ischaemic event, myocardial infarction, stroke, hemoptysis, hemotoncus, contusion, bleeding, blood vessel Complication, arteriospasm, arteriarctia, artery removing, perforation, lung perforation, false aneurysm, AV fistula；Allergic reaction, renal function Decline, pain, infection, Nausea and vomiting, fever, death, cardiopulmonary all standing, anxiolytic, anodyne habituation, in surgical procedure The relevant side effect of vasospasm medicine used in the relevant side effect of the anodyne used, surgical procedure and infection, poison Property, unfavorable hematology, bleeding, hemoptysis, the damage of Pyrogenicity, vascular wall or other body structures, pulmonary stenosis, nerve damage Wound, spasm, Aneurysmformation, aneurysm rupture, topography damage, plexus cardiacus damage, esophageal injury, tracheae damage Wound, injury of lungs, vagus nerve injury, bradycardia, tachycardia, part paralysis vocal cord, hemoptysis, decline in pulmonary function, hypertension, The relevant side effect of hypoperfusion or any combination thereof.

The some embodiments of present disclosure may include in the above advantage it is some, all or do not include.According to herein Included attached drawing, specification and claims, one or more technological merits are bright to those skilled in the art Aobvious.In addition, various embodiments may include in cited advantage although specific advantage is enumerated above It is whole, some or do not include.

Detailed description of the invention

Some embodiments of present disclosure are described herein with reference to attached drawing.The description allow to together with attached drawing how The some embodiments for practicing present disclosure become obvious to those of ordinary skill in the art.These figures are for illustration purposes only.

Fig. 1 is in accordance with some embodiments for improving the illustrative flow of the method for the ejection fraction of patient；With

Fig. 2 is the illustrative flow of the research of TROPHY 1 described in present example 1；

Fig. 3 A show denervation operation after 4 months mean pulmonary arterial pressure (mPAP) mean change (average value/ Standard error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；

Fig. 3 B show denervation operation after 4 months cardiac index mean change (average value/standard error； Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；

Fig. 3 C show denervation operation after 4 months pulmonary vascular resistance (PVR) mean change (average value/mark Quasi- error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；

Fig. 3 D show denervation operation after 4 months right arterial pressure (RAP) mean change (average value/standard Error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；

Fig. 4 A show denervation operation after 4 months quality of life (QoL) scoring mean change (average value/ Standard error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；

Fig. 4 B show 4 months after denervation operation 6 minutes travel distance (6MWD) mean change it is (average Value/standard error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004))；With

Fig. 4 C shows the flat of 4 months daily activities (mobility measure (actimetry)) after denervation operation Change (average value/standard error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004)).

Specific embodiment

In the following description, many aspects of present disclosure will be described.For illustrative purposes, it elaborates specifically to configure And details, in order to provide the thorough understanding of the different aspect to present disclosure.However, for those skilled in the art It is evident that present disclosure can be practiced in no detail given herein.Furthermore, it is possible to be omitted or simplified Well known feature, in order to avoid present disclosure is made to thicken.

Present disclosure generally relates to pulmonary artery denervations to penetrate blood system for improve patient with this need Number, the especially field of left ventricular ejection fraction.

According to some embodiments, the method is related to for artery manipulation device being located in the patient that for example ejection fraction reduces Pulmonary vasculature in target blood in or near, and using artery manipulation device weaken at least one sympathetic nerve, nerve The activity of fiber or neuron.The weakening of nerve, nerve fibre or neuron leads to the denervation of target blood, and therefore Lead to the improvement of ejection fraction.

According to some embodiments, sympathetic nerve and parasympathetic nerve can handle, it, can be in other alternate embodiments Only handle parasympathetic nerve.According to some embodiments, nerve can be handled in neuron-neuron level.According to some realities Example is applied, can handle entire nerve.For the purpose of present disclosure, phrase " nerve or neuron " can be used for handling one Or multiple complete nerves, one or more nerve fibres and/or one or more neurons.

According to some embodiments, neuron or nerve will be lowered simply.Alternatively, in further embodiments, passing through Innervation pulmonary vasculature can be related to partially or completely destroy one or more sympathetic nerve to reduce sympathetic tone.This The process for planting partially or completely nerve damage can be referred to as " denervation " or " making structure denervation " herein. For example, in some embodiments, treatment can be related to one or more artery (the such as, but not limited to pulmonary arteries for making to supply lung Dry, left pulmonary artery and/or right pulmonary artery) denervation.According to some embodiments, blood can will be made to return to heart from lung One or more vein denervations.It is this to adjust or reduce Sympathetic nerve by making pulmonary vasculature denervation The method of tension is a kind of unique method treating ejection fraction and being damaged.

As used herein, term " artery manipulation device " can refer to any dress for being configured as improving the ejection fraction of patient It sets.According to some embodiments, artery manipulation device may include or can be intravascular treatment device.According to some embodiments, Manipulation device may include the device for being configured as causing pulmonary artery denervation.

According to some embodiments, manipulation device may include radiofrequency launcher.According to some embodiments, pulmonary artery manipulation dress Setting may include the radiofrequency launcher improved.According to some embodiments, pulmonary artery manipulation device may include laser.

According to some embodiments, manipulation device may include conduit and be mounted on supravasal ultrasonic transmitter.According to one A little embodiments, supersonic beam can be unfocused supersonic beam.According to some embodiments, supersonic beam can be high intensity focused ultrasound Beam.According to some embodiments, supersonic beam can be low frequency ultrasound beam.It, can be with 1-50Mhz, 5- according to some embodiments 15Mhz, 8-12Mhz or any other suitable frequency emit supersonic beam.Every kind of possibility is all individual embodiment.

According to some embodiments, the length of conduit can be 100-150cm, such as, but not limited to about 120cm.

In some embodiments, in the range of the duration for the treatment of at each position was at such as 10-80 seconds, such as 20 Second, 40 seconds, 70 seconds or intermediate, shorter or longer time section.

In some embodiments, the ultrasound intensity applied is in the range of such as 30-70W/cm^2, such as 40W/cm^ 2,50W/cm^2,60W/cm^2 or centre, higher or lower intensity.

According to some embodiments, the method includes by pulmonary artery manipulation device be located in target blood or near.

As it is used herein, term " near " also refer to manipulation device contact target blood vessel or with target blood Wall is at a distance of 1mm, 2mm, 5mm, 1cm or more.Every kind of possibility is all individual embodiment.

According to some embodiments, therapeutic device is located in target blood to or can nearby be weakened at least one sympathetic mind Through, the activity of nerve fibre or neuron.According to some embodiments, weaken at least one sympathetic nerve, nerve fibre or nerve The activity of member can make target blood denervation, so as to improve the ejection fraction of patient.

In some embodiments, before treatment, later and/or period takes one or more of safety measure: In In some embodiments, conduit is only used for treatment single patient；In some embodiments, the disinfection again and/or again of conduit is avoided It is multiple to use；In some embodiments, conduit is only compatible with console (console) and is used together；In some embodiments, In It avoids that direct pressure is applied to escapement (distancing device) during the preparation process and/or the ultrasound of device is changed This method is executed while on energy device；In some embodiments, during treatment, if escapement is opened, conduit is avoided Manipulation and/or retraction；In some embodiments, in energy transmission process, conduit is not moved；In some embodiments, example In the case where also using other electric devices other than conduit during operation, by pulling up feed cable and/or recalling Conduit disconnects system；In some embodiments, in the case where escapement breaks down, escapement can be with conduit And/or it is retracted together with guide sheath；Carrying out X-ray examination inspection in some cases, it should be noted that avoid keeping patient excessively sudden and violent It is exposed to contrast agent；In some embodiments, before treatment, systemic anti-coagulants is provided for patient.Optionally, in therapeutic process Middle monitoring activated clotting time (activated clotting time, ACT).In some cases, it should keep at least 250 seconds ACT.In some embodiments, well-trained qualified medical personnel (for example, right cardiac catheterization expert) is only allowed to make With conduit and/or console；In some embodiments, during operation, Ying Keyong echocardiogram and be used for pericardial tamponade The device of diagnosis and the immediate treatment measure of (pericardial tamponade)；In some embodiments, it should be noted that avoid In uncontrolled inflammable detergent, anesthetic, nitrous oxide (N in closed type environment₂O electricity) or in the presence of oxygen is used The sub- medical treatment energy；In some embodiments, only just allow after training is completed using system；Pulmonary artery tissue dissection is occurring Or perforation is in some cases, answers significant care when being inserted into conduit；In some embodiments, conduit and/or other attachment (examples Such as, escapement) it will be disposed according to the hospital procedures of established biohazardous Waste disposal；In some embodiments In, only handle scheduled target region；It in some embodiments, can be before the surgery and/or in the process using electronic And/or automatic contrast medium injection device；Optionally, consider the specified setting delivered for flow injection and/or contrast agent；One In a little embodiments, water should be avoided and enter console；In some cases, if patient during treatment by degree pain, It is considered as analgesia and/or calmness；In some cases, if using radiography, radiation hazradial bundle should be handled.

According to some embodiments, this method further includes that one or more side effects are indicated on operation instructions.According to one A little embodiments, side effect can be selected from the groups being made up of: arrhythmia cordis, including bradycardia；Blood clot is formed and/or bolt Plug, may cause ischaemic event, such as myocardial infarction, stroke, hemoptysis (hemoptysis)；Hemotoncus, contusion, bleeding；Blood Pipe complication, including arteriospasm, arteriarctia, artery removing (arterial dissection), perforation, lung perforation, it is false Aneurysm, AV fistula；Complication relevant to contrast agent used in surgical procedure, such as under serious allergic reaction or renal function Drop；Pain；Infection；Nausea or vomiting；Fever；It is dead；Cardiopulmonary all standing；With contrast agent, arcotic used in surgical procedure, anti- Anxiety medicine, other anodyne and the relevant risk of vasospasm medicine；Biohazard: infection, toxicity, unfavorable hematology, allergy, Bleeding, hemoptysis, pain and Pyrogenicity risk；Damage of the energy transmission to vascular wall or other body structures, such as pulmonary artery Narrow, neurotrosis, spasm, Aneurysmformation or rupture；To topography such as plexus cardiacus, esophagus, tracheae, lung Or the damage for vagal accident/do not expect, lead to bradycardia, tachycardia, part paralysis vocal cord or hemoptysis (Haemoptysis)；Decline in pulmonary function；Hypertension；Hypoperfusion, or any combination thereof.Every kind of possibility is all individual reality Apply example.

As mentioned in this article, term " patient " and " subject " may be used interchangeably, and can be related to ejection fraction reduction Subject.

As used herein, term " ejection fraction " refers to the hundred of the blood pumped out from full ventricle with each heartbeat Divide ratio.According to some embodiments, ejection fraction can be left ventricular ejection fraction.According to some embodiments, ejection fraction can be with It is right ventricular ejection fraction.

According to some embodiments, ejection fraction reduction be can be defined as lower than 55%, lower than 50% or lower than 35% Ejection fraction.Every kind of possibility is all individual embodiment.

According to some embodiments, the patient that ejection fraction reduces may include across lung gradient (trans-pulmonary Gradient, TPG) increase and/or pulmonary vascular resistance (pulmonary vascular resistance, PVR) raised trouble Person.As used herein, term " across lung gradient " can refer to mean pulmonary arterial pressure (mPAP) and left atrial pressure (PLA；Usually pass through lung Capillary wedge pressure PCWP estimation) between difference.According to some embodiments, TPG increase can refer to mPAP-PCWP be more than 12 to 15mmHg.According to some embodiments, PVR raising can refer to higher than 2 wood's units (Wood unit), be higher than 2.5 wood's units, Higher than 3 wood's units or higher than the PVR of 3.5 wood's units.

According to some embodiments, improving ejection fraction may include that ejection fraction is made to increase by 5 percent or 10.

According to some embodiments, improving ejection fraction may include the lung blood at least one artery for reduce pulmonary vasculature Pipe resistance (PVR).

According to some embodiments, the PVR of patient is at least 2.5 wood's units.According to some embodiments, when reduction patient's When pulmonary capillary wedge pressure (PCWP), the PVR of patient keeps basic and becomes.According to some embodiments, when with diuretics and/or blood vessel When expanding medicine treatment patient, the PVR holding of patient is basically unchanged.

According to some embodiments, the activity for weakening at least one nerve, nerve fibre or neuron may include providing list Pole radio frequency, bipolar radio frequency, ultrasound, light, heat, cold emission, microwave radiation, phototherapy, magnetic therapy, electromagnetic radiation, electrotherapy, it is cold treat, etc. from Daughter therapy, mechanical handling, photodynamic therapy, core therapy, elasticity and hydrodynamic energy.

According to some embodiments, it may include dynamic from lung for weakening the activity of at least one nerve, nerve fibre or neuron Arteries and veins manipulation device emits supersonic beam.

According to some embodiments, the ejection fraction for improving patient includes increasing the cardiac index of patient.As used herein, art Language " cardiac index (cardiac index) " and " CI " are interchangeable, and refer to by one minute from left ventricle Cardiac output (cardiac output, CO) and body surface area (body surface area, BSA) associated hemodynamics Parameter is learned, to keep cardiac function associated with the size of individual.Measurement unit is every square metre of Liter Per Minute (L/min/m²)。 The normal range (NR) of cardiac index is 2.6-4.2L/min/m when rest (rest)²。

According to some embodiments, the ejection fraction for improving patient includes the right atrial pressure for increasing patient.As used herein, Term " right atrial pressure ", " RA pressure " and " RAP " interchangeably refer to the blood pressure in heart atrium dextrum.RAP reflects return Blood is pumped into the ability of arterial system by the blood volume and heart of heart.The normal range (NR) of RAP is 2-6mmHg or lower than 8mmHg.

According to some embodiments, the ejection fraction for improving patient causes quality of life (quality of life, QoL) to join Several improvement.The non-limiting example of suitable QoL parameter includes: that (patient is to its quality of life for quality of life (QoL) scoring Subjective evaluation)；6 minutes travel distances (6MWD), mobility measure (actimetry) (daily activity).

According to some embodiments, denervation treatment disclosed herein can improve the compliance of proximal end pulmonary artery, this Then right ventricular afterload can be reduced.

Referring now to Figure 1, it is in accordance with some embodiments for improving the explanation of the method 100 of the ejection fraction of patient Property flow chart.In step 110, pulmonary artery manipulation device is located in the pulmonary vasculature of patient of ejection fraction reduction In target blood.According to some embodiments, pulmonary artery manipulation device can be ultrasound transmission apparatus, such as substantially describe herein 's.In the step 120, weaken the activity of at least one sympathetic nerve, so that target blood denervation, so as to improve patient Ejection fraction.

Example

For example 1- in human research (TROPHY 1), pulmonary artery denervation improves ejection fraction

The research of TROPHY 1 is for carrying out the therapeutic of pulmonary artery denervation in the patient that ejection fraction reduces Intravascular ultrasound (TIVUS^TM) system clinical assessment.The summary of research is shown in the flowchart of fig. 2.15 patients are registered in In research, and PRELIMINARY RESULTS is obtained from three patients.The research is intended to directly and by evaluation of cardiac function, exercise tolerance (6 Minute travel distance) and quality of life questionnaire assessment lung denervation to the safety of ejection fraction, performance and initial effective Property.According to the explanation of manufacturer, (in the patient for meeting research standard) lung denervation branch is carried out in right, left and main pulmonary artery Match.The average time of denervation operation is 20-30 minutes, and the usability feedback of operator is excellent.According to specific trouble The quantity of the anatomical structure of person, the denervation position of each patient changes between 6 to 16.After operation, according to research side Case 1,4,8 and is assessed patient in 12 months after surgery.Preoperative and postoperative 1 and 12 months use MRI measure patient's Ejection fraction.Initial result (n=3) from follow-up in 1 month shows to penetrate blood system in lung denervation rear left and right ventricle Number averagely increases by 28%, as shown in table 1 below.

The ejection fraction based on MRI of the latter moon of sum before table 1- lung denervation

In follow-up in 4 months, all subjective and objective measurable parameters are improved.Fig. 3 A to Fig. 3 D is shown Mean change (the average value/standard error of 4 months hemodynamic parameters after denervation operation；Wilcoxon is examined 4M vs baseline；N=11 (not including patient 001-004)).

Advantageously, mean pulmonary arterial pressure (mPAP) reduces 13.5% (average value ± sd=-7.2 ± 6.6, p= 0.010), as shown in Figure 3A；Cardiac index increases 2% (average value ± sd=0.15 ± 0.52, p=0.695), such as Fig. 3 B institute Show；Pulmonary vascular resistance (PVR) reduces 15.0% (average value ± sd=-1.32 ± 0.98, p=0.003), as shown in Figure 3 C； And right arterial pressure reduces 20.5% (average value ± sd=-2.45 ± 3.5, p=0.053), as shown in Figure 3D.These results Show that ultrasonic therapy can improve proximal end pulmonary artery compliance in Therapeutic vascular, to reduce right ventricular afterload.

Fig. 4 A to Fig. 4 C shows that the mean change of 4 months quality of life (QoL) parameter after denervation operation is (flat Mean value/standard error；Wilcoxon examines 4M vs baseline；N=11 (not including patient 001-004)).

Advantageously, it observes (flat by the positive variation of the EmpHasis-10 life quality scores (QoL) for reducing by 21% instruction Mean value ± sd=-6.9 ± 14, p=0.275), as shown in Figure 4 A.Moreover, it was similarly observed that 6 minutes travel distance (6MWD) mention High 40 meters (21%) (average value ± sd=45.5 ± 64.6, p=0.065), as shown in Figure 4 B, and daily activity is (living Dynamic degree measurement) 12% (average value ± sd=584 ± 883, p=0.141) is improved, as shown in Figure 4 C.

Examples detailed above is non-limited example, and be not intended to limit scope of the present disclosure.Described example can To include different features, and not all, of the features is all required in all embodiments of present disclosure.

Term as used herein is not intended to be limiting merely for for the purpose of describing particular embodiments.As herein Used, the noun that unused numeral-classifier compound limits also is intended to include plural form, unless the context clearly indicates otherwise.It will further manage Solution, when using term " includes " or "comprising" in the present specification, it is specified exist the feature pointed out, integer, step, Operation, element or component, but do not prevent or exclude one or more of the other feature, integer, step, operation, element, component or Its presence or addition for organizing.

In the description and claims of this application, each of word "include", "comprise" and " having " and Its form is not necessarily limited in list may associated member with the word.

Although many illustrative aspects and embodiment is discussed above, those skilled in the art will appreciate that its Certain modifications, displacement, addition and sub-portfolio.Accordingly, it is intended to by appended claims and claims hereafter introduceds book solution It is interpreted as including all such modifications, displacement, addition and sub-portfolio in its true spirit and range.