Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: Results from the Euro-ASA registry

1
Long-term clinical outcome after alcohol septal
ablation for obstructive hypertrophic
cardiomyopathy Results from the Euro-ASA
registry

• Veselka J, Jensen MK, Liebregts M, Januska J,
  Krejci J, Bartel T, Dabrowski M, Hansen PR,
  Almaas VM, Seggewiss H, Horstkotte D, Tomasov P,
  Adlova R, Bundgaard H, Steggerda R, ten Berg J,
  Faber L
• on behalf of the Euro-ASA Registry

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Introduction

• Hypertrophic cardiomyopathy (HCM) is
  characterized by the presence of increased
  thickness of the left ventricular wall that is
  not solely explained by abnormal loading
  conditions, including hypertension and/or
  valvular diseases.
• Two-thirds of patients with HCM have evidence of
  left ventricular outflow obstruction.

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Background

• ASA was introduced two decades ago by Ulrich
  Sigwart in The Lancet as an alternative
  percutaneous technique of obstruction.

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Background
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Aim

• Although encouraging results of single-centre or
  national ASA registries have been repeatedly
  published, long-term safety and efficacy of the
  procedure were still debated over the following
  decades.
• In this study, we wanted to determine
• i) survival and clinical outcome in patients
  treated with ASA,
• ii) predictors of mortality events and clinical
  outcome,
• iii) relationships between alcohol dose injected
  during ASA, improvement of LV outflow tract
  pressure gradient and the occurrence of complete
  heart block.

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Patients and follow-up

• A total of 1275 (5814 years, 49 females),
  highly symptomatic, consecutive patients treated
  with ASA were included.
• Ablations were performed in 10 centres from 7
  European between January 1996 and February 2015.
• The median of follow-up for survival was 5.0 (IQR
  2.18.2) years.

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Baseline characteristics/follow-up
Baseline Follow-up P-value
Age, years 58 14 63 13
Dyspnoea, NYHA class 2.9 0.5 1.6 0.7 lt0.001
Angina, CCS class 1.3 1.2 0.7 0.8 lt0.001
Episodes of syncope, 22 7 lt0.001
Left ventricular outflow gradient, mmHg 67 36 16 21 lt0.001
Left ventricular diameter, mm 43 6 46 6 lt0.001
Left ventricular ejection fraction, 70 10 66 10 lt0.001
Basal septum thickness, mm 20 4 15 4 lt0.001
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Peri-procedural complications

• A total of 13 (1) patients died within 1 month
  after ASA
• heart failure, pulmonary embolism, cardiac
  tamponade, sepsis, stroke, carcinoma, sudden
  death.
• Intra-procedural or early post-procedural (2
  days) sustained VT/VF requiring electrical
  cardioversion occurred in 16 patients (1.3).

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Complete heart block

• Mainly transient intra-procedural complete heart
  block occurred in 468 (37) patients.
• A total of 151 (12) patients subsequently
  required permanent pacemaker implantation.

Higher doses of alcohol were associated with a
higher occurrence of the complete heart block (HR
119, 95 CI 105-135 p0006)
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Redo procedures

• Until the last clinical check-up,
• 87 (7) patients underwent re-ASA procedure
• 42 (3) patients primarily treated by ASA
  subsequently underwent myectomy.

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Relationship between alcohol dose, relative delta
pressure gradient and complete heart block

• Volumes of injected alcohol were 2.20.9 (range
  0.411) ml.

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• The relative delta pressure gradient was
  independently associated with
• the amount of injected alcohol (HR 177, 95 CI
  107-247 plt0001)
• septum thickness at the last clinical check-up
  (HR -021, -005- -037 p lt0001)
• NYHA class at the last check-up (HR -143, 95 CI
  -244-043 p 0005)

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Clinical efficacy

• At the last clinical check-up (median 39 IQR
  1474 years)
• ASA reduced
• NYHA class from 2.90.5 to 1.60.7 (plt0.001)
• LV gradient from 6736 to 1621 mmHg (plt0.001)
• 89 of patients reported dyspnoea of NYHA class
  1 or 2
• 86 of patients experienced improvement of 1
  class of NYHA

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Clinical efficacy

• Lower LV outflow tract gradient at the last
  clinical check-up was independently associated
  with the final NYHA class 2 (HR 0.98, 95 CI
  0.970.99 plt0.01).

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All-cause mortality(95 confidence intervals)
A total of 171 (13) patients died during 7057
patient-years of follow-up, indicating a post-ASA
all-cause mortality rate of 2.42 (95 CI,
2.072.82) deaths per 100 patient-years.
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Predictors of all-cause mortality

• Independent predictors of all-cause mortality
  were
• higher age at ASA (HR 1.06, 95 CI 1.051.08
  plt0.01),
• septum thickness before ASA (HR 1.05, 95 CI
  1.011.09 plt0.01),
• NYHA class before ASA (HR 1.5, 95 CI 1.002.10
  p0.047)
• all-cause mortality was associated with the LV
  gradient at the last check-up (HR 1.01, 95 CI
  1.001.01 p0.048).

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Survival of patients divided in three groups
according to LV gradient at the last clinical
check-up
After adjustment for age at ASA, septum thickness
before ASA and NYHA class before ASA, 10-year
all-cause mortality rates were 75, 72, and 55,
respectively
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Mortality events (all-cause deaths, appropriate
ICD discharges, resuscitations) (95 confidence
intervals)
A total of 197 (15) patients experienced
all-cause death or appropriate ICD discharge
during 7055 patient-years of follow-up,
indicating the rate of mortality events as 2.84
(95 CI, 2.463.27) per 100 patient-years).
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Predictors of mortality events

• Independent predictors of mortality events were
• higher age at ASA (HR 1.05, 95 CI 1.041.07 p
  lt0.001)
• septum thickness before ASA (HR 1.06, 95 CI,
  1.031.1 p0.001)
• mortality events were independently associated
  with the LV gradient at the last clinical
  check-up (HR 1.01, 95 CI 1.001.01 p0.02).

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Sudden mortality events (95 confidence
intervals)
Sudden mortality events (sudden death, first
appropriate ICD discharge or successful
resuscitation) occurred in 68 (5.3) patients,
indicating the rate as 0.98 (95 CI, 0.761.12)
per 100 patient-years.
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Predictors of sudden mortality events

• The only independent predictor was the septum
  thickness before ASA (HR 1.07, 95 CI 1.011.12
  p0.014).

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Survival rates
Survival rates (95 CI) 1 year 3 years 5 years 10 years Survival rates (95 CI) 1 year 3 years 5 years 10 years Survival rates (95 CI) 1 year 3 years 5 years 10 years Survival rates (95 CI) 1 year 3 years 5 years 10 years Survival rates (95 CI) 1 year 3 years 5 years 10 years
All-cause death 98 (96-98) 94 (93-95) 89 (87-91) 77 (73-80)
All-cause death or appropriate ICD discharge 97 (96-98) 92 (90-94) 87 (85-89) 73 (69-77)
Sudden mortality event 99 (98-99) 97 (95-98) 95 (93-96) 90 (88-93)
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Causes of death
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Conclusions

• Higher doses of alcohol are more effective in
  decreasing LV outflow tract gradient, but are
  also associated with a higher occurrence of
  peri-procedural complete heart block (new
  finding).
• A more pronounced reduction of LV outflow tract
  gradient is independently associated with a lower
  resultant NYHA class (new finding).
• The all-cause mortality and all mortality events
  are independently associated with the residual LV
  gradient (new finding).

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Conclusions

• The 30-day post-procedural mortality is 1, and
  12 of treated patients require an early
  post-procedural pacemaker implantation.
• LV outflow gradient is lowered by 76, and 86 of
  patients experience improvement of 1 class of
  NYHA.
• The annual post-ASA mortality rate is 2.4 and
  the risk of a sudden mortality event is 1 per
  year.

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Take-home messages

• Alcohol septal ablation performed in dedicated
  centres is a safe and effective procedure for
  highly symptomatic obstructive HCM patients.
• The post-ASA residual obstruction is a
  significant factor influencing both long-term
  functional status and survival (new finding).
• Appropriate pre-procedural patient selection and
  elimination of the LV outflow obstruction should
  be pursued in these patients.

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U. Sigwart. Lancet 1995

• diminishing the outflow tract gradient in
  patients with symptoms may greatly improve
  quality of life and reduce symptoms.
• There is not the slightest evidence that this
  procedure will lead to acceleration of left
  ventricular failure

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Acknowledgment
Department of Cardiology, 2nd Medical School,
Charles University, University Hospital Motol,
Prague, Czech Republic. Department of Cardiology,
Heart and Diabetes Center NRW, Ruhr-University
Bochum, Bad Oyenhausen, Germany. Department of
Cardiology, Copenhagen University Hospital, The
Heart Center, Rigshospitalet, Copenhagen,
Denmark. Department of Cardiology, St. Antonius
Hospital Nieuwegein, Nieuwegein, the Netherlands.
Cardiocentre Podlesí, Trinec, Czech Republic. 1st
Department of Internal Medicine /
Cardioangiology, St. Annes University Hospital
and Masaryk University, Brno, Czech Republic.
Department of Internal Medicine III, Medical
University Innsbruck, Austria. Department of
Interventional Cardiology and Angiology,
Institute of Cardiology, Warsaw, Poland.
Department of Cardiology, Gentofte Hospital,
Copenhagen University Hospital, Hellerup,
Denmark. Department of Cardiology, Oslo
University Hospital, Oslo, Norway.