Abstract of medical PHD thesis: The clinical characteristics andefficacy ofinfrapopliteal percutaneous transluminal angioplasty in patient with lower extremity arterial disease

The proceed subject with two purposes: Study on clinical characteristics of lower extemity arterial disease with infrapopliteal lesions. Evaluate mid-term outcomes and factors influencing clinical outcomes of infrapopliteal angioplasty in patient with lower extremity arterial disease.

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LUONG TUAN ANH

THE CLINICAL CHARACTERISTICS ANDEFFICACY

OFINFRAPOPLITEAL PERCUTANEOUS

TRANSLUMINAL ANGIOPLASTY IN PATIENT WITH LOWER EXTREMITY ARTERIAL DISEASE

Speciality: Cardiology Code: 62.72.01.41

ABSTRACT OF MEDICAL PHD THESIS

Hanoi – 2019

MEDICAL AND PHARMACEUTICAL SCIENCES

Supervisor:

1 Ass.Prof.PhD Le Van Truong

2 Ass.Prof.PhD Vu Dien Bien

Day Month Year 2019

The thesis can be found at:

1 National Library of Vietnam

2 Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences

INTRODUCTION

Lower extremity arterial disease (LEAD) is very common, prevalence 3-7% of the population, 20% in people over 75 years old Ulcers and gangrenelower limb is the end- stages of the disease, threatened amputation, loss of limb functiondue to infrapopliteal arterial lesions Below the knee revascularizationis the most important in limb salvage for this disease

There are two methods of infrapopliteal arterial revascularization: bypass surgery and percutaneous angioplasty, so bypass surgery is difficult due to below the knee artery small, long lesions, bad run-off, elderly patients, many serious diseases combined Percutaneous transluminal angioplasty (PTA)is becoming

as important treatments for this area

Currently LEAD with infrapopliteal lesions was concerned, innitial step was deployed in Vietnam, yet researchs on medium and long-term effectiveness, small sizes, should we proceed subject with two purposes:

1 Study on clinical characteristics of lower extemity arterial disease with infrapopliteal lesions

2 Evaluate mid-term outcomes and factors influencing clinical outcomes of infrapopliteal angioplasty in patient with lower extremity arterial disease

Chapter 1 OVERVIEW 1.1 LEAD Concept

Lower extremity arterial disease (LEAD) is only partially or entirely in the lower limbs is not provided with adequate blood, responding to physiological activities, with a duration of time more than two weeks This concept excludes acute limb ischemia, vessel wounds, vascular complications

The cause of LEAD is the development of atherosclerotic plaques, which cause a narrowing or complete blockage of the limb vessels

Below the knee (BTK) arteriesincludes tibial artery (aterior tibial artery, posterior tibial artery, peroneal artery), pedal artery (dorsal pedal artery, medial plantar artery, lateral plantar artery)

1.2 Clinical Characteristics of LEAD

LEAD progresses through several stages, from asymptomatic, claudication, rest pain, ulcer and gangrene Critical limb ischemia (CLI, including rest pain, ulcer and gangrene lower limb) with infrapopliteal arterial lesion, considered the end stage of the LEAD, threaten to limb losss

LEAD is a common chronic cardiovascular disease caused by atherosclerosis, with coronary artery disease and stroke, the prevalence of 3-7% of the population (20% in people over 70 years of age), of which the rate of CLI is 1 % population

Common risk factors of LEAD are elderly age (> 50 years), smoking, diabetes, hypertension, and dyslipidemia

Table 1.2 Rutherford classification of PAD

Grade Category Clinical

In which the diagnostics tests are used in Vietnam are measuring ABI index, ultrasound of lower extremities arterial lesions, CTA before percutaneous transluminal angioplasty, and angiography in intervention procedure

1.4 PTA of LEAD with Infrapopliteal lesions

1.4.1 Treatment Purposes

+ Reduce symptoms of limb ischemia

+ Limb salvage

+ Multi-level of lower extremity arterial lesion

Aortoiliac lesions: aorto-iliac occlusion, aorto-iliac stenosis

in patient when life expectancy is not over 2 years

Femoro-popliteal lesions: short lesions (< 25cm), long lesions (≥ 25cm) in patient when life expectancy is not over 2 years

1.4.3 Techniques of infrapopliteal revascularization

There are currently two techniques of infrapopliteal revascularization are: balloon angioplasty (plain balloon, drug coated balloon), stenting (covered and uncovered stent), with specified is:

+ Balloon angioplasty is the priority technique

+ Stenting if the ballooning is not effective

BTK intervention is considered to be a revascularization method with a high effectiveness of limb preservation, less complications than bypass surgery In which, plain ballooning is the priority method, assessing the effectiveness of normal ballooning with different types of infrapopliteal lesions as well as combining with additional techniques (drug-coated balls, atherectomy, .) in order to reduce the rate of restenosis is still needing further research to confirm the effect

Chapter 2 SUBJECTS AND METHODS 2.1 RESEARCH SUBJECTS

85 patients with 91 infrapopliteal arterial lesions, were reperfusioned by PTA in 108 hospital from May 2011 to June 2016

- Patients agree to participate in the research

2.1.2 Exclusion criteria

- Acute limb ischemia (ALI)

- Non-atherosclerosis LEAD (Takayasu, Bueger, Raynaud, )

- Infrapopliteal arterial stenosis or occlusion due to external causes of vessel (tumor, trauma, )

- Venous disease of lower limbs (varicose veins, venous thrombosis, )

- Peripheral neuropathy of lower limb (peripheral neuritis, peripheral neuropathy due to diabetes, )

- Severe disease (liver failure, renal failure, heart failure, acute myocardial infarction, stroke, severe infections)

2.2 RESEARCH METHOD

2.2.1 Study design: prospective, intervention, follow-up

2.2.2 Research steps

2.2.2.1 Before lower limb PTA

Patients should be screened and tested for investigation eligibility Patients meet inclusion criteria will be asked to participate

in this research

+ Clinical examination: finding limb ischemia, duration of illness, cardiovascular risk factors (old age, diabetes, hypertension, smoking, metabolic lipid disorders, coronary artery disease, stroke, )

+Laboratory tests:

- Blood tests: blood formulation, coagulation tests (Prothrombin, INR, APTT, Fibrinogen), blood biochemistry tests (Ure, Creatinine, Lipid, Protid, Albumin, Bilirubin, SGOT, SGPT, electrolytes), immunity tests (HBsAg, anti-HIV, anti-HCV)

- Cardiopulmonary X-ray, ECG, echocardiography

- ABI index

ABI measured by Doppler handheld smartdrop 45 (Japan), from

2011 to 2013, when we did not have automatic ABI meter and by ABI automatic ABI meter VP1000 Plus (OMRON, Japan), from

Iliac artery lesion and femoral artery lesion were revascularized before infrapopliteal artery lesion It will be possible to open lesions in one or two sessions, depending on each patient

+ Patient preparation: patients being screened, tested and explained deeply about disease and treatment method Patients was asked to sign an informed consent, do not eating and drinking at least 6h before procedure

+ Interventional procedure of iliac and femoral artery occlusion

- Anesthesia: local anesthesia with 5-10ml lidocaine 2% in vascular access

- Patient posture: lying on the back

- Vascular access: common femoral artery or brachial artery

- Giving the catheter to the iliac and femoral artery occlusions, taking assessments the lesion, collateral branches and run-off

- Going through the occlusion by guidewire 0.035 inches, with intraluminal technique or subintimal technique (in case CTO over 3 months) We could use additional support catheters to increase the ability to pass through the complicated occlusion

- Open the occlusion by dilating balloon 6F, 6atm pressure, keeping 30s, then we do angiography after deflating balloon.Finishing procedure if the recurrence stenosis under 50% diameter, on the otherwhile choosing the bigger balloon or stenting when balloon failure

+ Infrapopliteal PTA

- Anesthesia: spinal anesthesia at L4-L5

- Patient posture: lying on the back

- Vascular access: femoral artery in the side of infrapopliteal lesion

- Evaluating the lesions of iliac and femoral artery, collateral circulation and run-off before intervention

- Revascularization femoral and popliteal artery occlusion (see above)

- Giving guiding catheter to popliteal artery Going through antegrade the infrapopliteal artery lesions by support catheter TrailBlazer 4F (Boston, USA), Controlwire 18 (Boston, USA) When failure, we could go retrograde from tibial artery or pedal artery, with sheath 4F

- Dilating the occlusions by balloon 3-3.5 mm diameter for tibial artery and balloon 2-2.5 mm diameter for pedal artery, with 100-200

in length Keeping dilation from 30s to 2 minutes, from 6 to 14 atm pressure

- We do angiography after deflating balloon Finishing procedure if the recurrence stenosis under 50% diameter, on the otherwhile ballooning again with a more suitable size balloon

2.2.2.3 Follow-up after PTA

- Clinical follow-up (FU), re-do all biochemical, hematological after PTA Well treatment for patient until being discharged

- Measuring ABI and lower extremity arteries ultrasound after 1 day Amputation gangrene and discharge

- Periodic follow-up 1, 3, 6 and 12 months after procedure include clinical examination, ABI measurement, ultrasound, and assessment of

- Effectiveness on pain relief, improve walking distance

- Wound healing (WH), limb salvage

- Complications: hematoma, distal thrombosis, peritoneal bleeding, acute renal failure,

- Mortality: death rate after procedure 1 month, 3 months, 6 months and 12 months

- Restenosis and reocclusionafter procedure 1 month, 3 months, 6 months and 12 months

- Factors influencing clinical outcomes of infrapopliteal angioplasty risk factors, lower extremity artery lesions, techniques and strategies.(direct / indirect angiosome (DR/IR), 1-tibial / 2-tibial arteries revascularization)

2.3 DATA PROCESSING

- The research data is processed by medical statictic method with SPSS 20.0 software for Window

Chapter 3 RESEARCH RESULTS 3.1 GENERAL CHARACTERISTICS

3.1.1 Clinical characteristics

- Mean age was 75.6, the age group ≥80 was 40% Male 67.1%, female 32.9%.Risk factors werehypertension (64.7%), diabetes (25.9%), metaboliclipid disorder (25.9%), smoking (24.7%).Clinical stages were Rutherford 5 (45.1%) and Rutherford 4 (30.8%) Ulcers and gangrene in toes (45.1%) wasmost common

3.1.2 Subclinical characteristics

- Mean ABI was 0.56, group ABI 0.4-0.75 was most common (38%) The artery lesion was majority arefemoral, popliteal–infrapopliteal level (53.8%) and infrapopliteal level (38.5%) Mean tibial artery lesion length was 20.4 cm Infrapopliteal artery lesion classification was TASC D (97.8%)

3.2 TECHNICAL CHARACTERISTICS AND CLINICAL OUTCOMES OF INFRAPOPLITEAL PTA

3.2.1 Technical characteristics

- Most common vascular access was from the ipsilateralfemoral at the infrapopliteal lesion side (97.8%) Antegrade revascularization was 86.8% Intraluminal technique was 54.6% (subintimal technique was 45.2%) 1 tibial artery revascularization rate was 58.2%, 2 tibial artery revascularization was 35.2% Direct angiosome was 70.2%

- Complications rate was 3.3% (3 cases with mild clinical symptom, recovered rapidly 1 case hematoma, 1 case distal thrombosis and 1 case peritoneal bleeding must be open sugery)

3.2.2 Clinical Outcomes of Infrapopliteal PTA

Table 3.19.Success rate Success accessment Number of success %

Duration of wound healing(month) = 3.1 1.8

Conclusion: Wound healing time was 27.1%, 72.3% and 100% after

1 month, 3 months and 6 months respectively.Mean duration of wound healingwas 3.1  1.8 months

Table 3.26.Wound healing and reperfusion

Reperfusion (1) p

DR (n, %)

IR (n, %)

(62.9)

13 (100)

(22.9)

5 (41.7) Conclusion: Reperfusion properties (direct/indirect angiosome) affectthe rate of woung healing after 1 month (p < 0.05)

Table 3.27.Wound healing time and reperfusion

Reperfusion Wound healing time(month) p

% Amputation rate 12 13.2

Chart 3.6.InfrapoplitelPTA restenosis

Conclusion: Restenosis rate of infrapopliteal PTA was 34.1%, 50%, 65.9% after 3 months, 6 months, 12 months respectively

Bảng 3.30.Restenosis and Clinical stages

11 (39.3)

10 (25.6)

5 (62.5) p 1-2

> 0.05

(0)

9 (75)

17 (60.7)

29 (74.4)

3 (37.5)

13 (46.4)

19 (48.7)

7 (87.5) p 1-3

> 0.05

(0)

8 (66.7)

15 (53.6)

20 (51.3)

1 (12.5)

19 (67.9)

26 (66.7)

8

1-4< 0.05

(0)

8 (66.7)

9 (32.1)

13 (33.3)

0 (0)

Conclusion: The more severe clinical stages, the higher infrapopliteal restenosis rate Restenosis rate of infrapopliteal PTA after 12 months was 33.3%, 67.9%, 66.7%, 100% of Rutherford 3, Rutherford 4, Rutherford 5, Rutherford 6 respectively

Chart 3.7.Infrapoplitel PTA reocclusion

Conclusion: Reocclusion rate of infrapopliteal PTA was 18.2%, 25%, 35.6% after 3 months, 6 months, 12 months respectively

Table 3.34.Infrapoplitealreintervention Re-intervention rate

Mean duration time of reintervention (month) = 6.0  2.5

Conclusion:Re-intervention rate of infrapopliteal PTA was 14.8%, 19.8% after 6 months, 12 months respectively Mean duration time

of re-intervention was 6.0  2.5 months

Table 3.35.Mortality of infrapopliteal PTA Mortality 1 month FU

3.3 FACTORS INFLUENCING CLINICAL OUTCOMES

3.3.1 Affection of clinical factors

Table 3.36.Clinical stages and clinical outcomes

3 (10.7)

12 (29.3)

5 (55.6) p1-

2< 0.05

(0)

11 (91.7)

25 (89.3)

29 (70.7)

4 (44.4)

0 (0)

2 (4,9)

1 (11,1) p1-

3> 0.05

(100)

12 (100)

28 (100)

39 (95.1)

8 (88.9)

28 (100)

38 (92.7)

9 (100) p1-

4> 0.05

(0)

0 (0)

0 (0)

3 (7,3)

0 (0)

Conclusion: The more severe clinical stages, the lower success rate

of hemodynamics Success rate of hemodynamics was 91.7%, 89.3%, 70.7%, 44.4% of Rutherford 3, Rutherford 4, Rutherford 5, Rutherford 6 respectively

Table 3.39.Arterial lesion levels and outcomes

Single- level (n, %)

Multi- level (n, %)

(40)

8 (14.3)

(2.9)

2 (3.6)

(97.1)

54 (96.4)

(100)

49 (90.7)

(97.1)

42 (77.8)

(93.9)

38 (71.7)

Sum 33 53

Conclusion: Multi-level arterial lesion was higher than single-level arterial lesion in hemodynamic success rate (OR = 4), reintervention6 months FU (OR = 17.3), reintervention 12 months

FU (OR = 6.1)

3.3.2 Affection of revascularization strategy

Table 3.40.Number of tibial artery revascularization and outcomes

Number of tibial artery revascularization(1)

p

1 tibial artery (n, %)

≥2tibialartery (n, %)

(50)

27 (84.4)

(18.8)

10 (32.3)

(74.2)

35 (61.4)

(58.1)

26 (45.6)

(45.2)

16 (28.1)

Conclusion: Wound healing rate after 1 month of 1 tibial artery group was higher than ≥ 2 tibial artery group, 50% vs 15.6% respectively, OR = 5.4