1) The document describes a randomized controlled trial called ISCHEMIA-CKD that compared an invasive strategy (PCI or CABG) to a conservative strategy in patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia. 2) The trial found that an initial invasive strategy did not result in a lower rate of death or nonfatal myocardial infarction compared to an initial conservative strategy. 3) Limitations of the trial included exclusion of very symptomatic patients and lower than expected event rates, reducing the power to detect differences between strategies.

1. JOURNAL
REVIEW
27/04/2020
Dr Sravan kumar G
Senior Resident
Department of
Cardiology,
SCTIMST

4. BACKGROUND
 Cardiovascular disease is leading cause of death in CKD
 Presence of Kidney disease – Angiography & Revascularisation –
Increases risk of procedural complications
 Whether these procedural risks is associated with long term
benefit ? Unknown
 Most trials exclude Patients with advanced kidney disease

5. AIM
 ISCHEMIA-CKD (International Study of Comparative Health
Effectiveness with Medical and InvasiveApproaches – Chronic
Kidney Disease) to test whether there is incremental benefit of an
invasive strategy(PCI or CABG) in patients with stable coronary
disease and advanced chronic kidney disease.

6. STUDY
DESIGN
International, Randomized
comparative effectiveness
trial, Parallel to Ischemia trial

7.  STUDY DESIGN
 international, randomized trial,
30 countries
92 cases from
INDIA
Study
population

8. Inclusion Criteria:
• At least moderate ischemia on an exercise or pharmacologic stress test
• End-stage renal disease on dialysis or estimated glomerular filtration rate
(eGFR) <30mL/min/1.73m2
• Age ≥ 21 years
Exclusion Criteria:
 Left ventricular EF < 35%
 History of unprotected left main stenosis >50% on prior CCTA or prior cardiac
catheterization (if available)
 Finding of “no obstructive coronary artery disease ” (<50% stenosis in all major epicardial
vessels) on prior CCTA or prior catheterization, performed within 12 months
 Acute coronary syndrome within the previous 2 months
 PCI within the previous 12 months
 NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart
failure within the previous 6 months
 Coronary anatomy unsuitable for either percutaneous coronary intervention (PCI) or
coronary artery bypass grafting (CABG)
 Unacceptable level of angina despite maximal medical therapy

11. Unstable angina
Myocardial infarction
Ischemic heart failure
Resuscitated sudden cardiac
arrest
Angina refractory to medical
therapy

13. Follow up: 1.5, 3, 6, and 12 months after randomization during the first year
and every 6 months thereafter.

15. Outcomes
 Primary outcome
 Composite of death or
 Nonfatal myocardial infarction
 Secondary outcome
 Composite of death
 Nonfatal myocardial infarction
 Hospitalization for unstable angina
 Heart failure
 Resuscitated cardiac arrest
 Safety outcomes were
 Initiation of dialysis in patients who were not receiving
dialysis at baseline and
 Composite of newly initiated dialysis or death.

28. Discussion
 In this trial involving patients with stable coronary disease,
advanced kidney disease, and moderate or severe ischemia, initial
invasive strategy did not result in a lower incidence of death or
nonfatal myocardial infarction than an initial conservative strategy

29. Discussion
 Coronary angiography was performed in approximately 85% of
the patients who were assigned to be treated with the invasive
strategy, whereas revascularization was performed in only 50%
 absence of obstructive coronary disease (101 patients (1/4 of
Invasive strategy)
 reduced accuracy of stress testing
 greater prevalence of microvascular disease in patients with advanced
kidney disease
 CCTA was not performed

31. Limitations
 Very symptomatic
 heart failure
 recent acute coronary syndromes
 EF < 35% were excluded from the trial, so the findings do not
extend to such patients
 Event rates were lower than projected, and together with a low
incidence of revascularization in the invasive-strategy group (50%)
and an 11% incidence of revascularization before a confirmed
event in the conservative-strategy group, the trial had less power
than anticipated to show a benefit for the invasive strategy
 Contrast-associated acute kidney injury was reported at each trial
site and was not centrally adjudicated

34. Introduction
 Andreas Grüntzig - percutaneous transluminal coronary
angioplasty (PTCA) in 1971
 BMS - 1987
 complicated by an unacceptably high rate of acute and
subacute vascular closure
 introduction of dual platelet aggregation inhibition in
the mid 1990s, stent implantation became a safe
procedure
 high restenosis rate with BMS was finally able to be
reduced by local drug delivery from drug-eluting stents
(DES)
 High rates (twice) of MI 9 years after with BMS vs
PTCA, even DES > Angioplasty

35. Study design
 210 patients with NSTEMI
 Randomised, controlled, non-inferiority, multicentre
trial
 Comparing a paclitaxel iopromide-coated DCB
(SeQuent® Please and SeQuent® Please NEO, coated
with 3 μg paclitaxel/mm² of balloon surface; B. Braun
Melsungen AG, Berlin, Germany) with primary stent
treatment (BMS or Limus-eluting DES).
 Study period – Dec 2012 to Jan 2017
 Study place – Germany (5 centres)

36. Inclusion
Criteria
 NSTEMI defined by
 ischaemic symptoms (angina pectoris) >30 minutes, last
symptoms within 72 hours before randomisation,
 positive cardiac troponinT, I, or hs-troponin above the
99thpercentile
 Identifiable culprit lesion without angiographic
evidence of large thrombus with intended early
percutaneous coronary intervention (PCI)
 Diameter stenosis > 70%/TIMI flow <3, vessel diameter
2.5 – 3.5mm

37. Exclusion
Criteria
 Cardiogenic shock
 STEMI
 No identifiable culprit lesion
 In-stent restenosis lesions
 Indication for acute bypass surgery
 Culprit lesion in a venous bypass graft
 Contraindication for treatment with heparin, ASA and
thienopyridines, other medical illness

38. Procedure
 Dual antiplatelet therapy with aspirin plus clopidogrel,
ticagrelor or prasugrel was continued orally for 12
months
 clinical follow-up at 30 days, four months, and nine
months post procedure

41.  Primary Endpoint
 Target lesion failure(TLF) combined clinical endpoint consisting of
cardiac or unknown death, myocardial reinfarction, and target
lesion revascularisation after 9 months
 Secondary endpoints
 total major adverse cardiovascular events (MACE)
 all-cause mortality
 myocardial infarction
 target lesion revascularisation
 Stroke
 PCI at other vessels
Endpoints

42. RESULTS

47. Discussion
 Despite the lack of larger randomised trials on the preferred
interventional technique, DES are regarded as the standard of
care in most countries for NSTEMI
 Increased risk of thrombotic complications in acute coronary
syndrome is a striking argument to avoid permanent implants
 Main contraindications for DCB treatment
 flow-limiting dissections
 unsatisfactory initial lumen gain

48. Discussion
 The early reduction of vascular occlusions after stent implantation
is related to the fixation of flow-limiting dissections, which are
rare
 Prevention of acute and subacute stent thrombosis is based
mainly on the initiation of dual antiplatelet therapy
 For balloon angioplasty alone, the impact of this drug treatment
has never been systematically investigated

49. Discussion
 The special feature of the “DCB only” treatment is that it results in
lumen enlargement after a few months post treatment, which can
be considered a type of vascular restoration

50. Limitations
 lesions with a high thrombus burden were excluded
 Initially BMS later DES were included
 Small number

53. Conclusion
 In patients with NSTEMI, treatment of coronary de
novo lesions with DCB was non-inferior to stenting
with BMS or DES

55. Introduction
 CRT - Electrical dyssynchrony and reduced systemic
ventricle ejection fraction
 In children and patients with CHD, a number of
retrospective studies have demonstrated acute and
mid-term improvement in EF and in QRS duration
(QRSd) but there are no trials evaluating survival
benefit of CRT in these patient groups

56. Study design
 Retrospective propensity score matched study
 Primary end point
 Transplant free survival

57. Inclusion
Criteria
 Age<21 years and/or CHD who underwent CRT at Lucile
Packard Children’s Hospital and Stanford Healthcare
between Jan 1st 2004 and December 31st 2017
 Systemic SVEF <45%
 Symptomatic heart failure [defined as American Heart
Association Stage C or D]
 Electrical dyssynchrony [defined as either a QRSd z-
score≥3 or, in paced patients, a ventricular pacing
burden (Vp) ≥40%]

58. Exclusion
criteria
 Eisenmenger syndrome
 Current ventricular assist device
 Previous heart transplant
 Weight <4kg.

59. Controls
 Pediatric and/or CHD patients who never received CRT
and who met the same inclusion and exclusion criteria
at an outpatient clinical encounter within the same
time period

60.  CRT:Multi-site ventricular pacing system implanted with at least
one pacing lead to the systemic ventricle (SV).
 CHD: CHD other than isolated bicuspid aortic valve, patent
foramen ovale or patent ductus arteriosus

61. Selection of
Cases &
Controls
 Cases Selection: institutional pacing databases, on day
of CRT
 Control Selection:comprehensive screening cohort
with low SVEF and electrical dyssynchrony was
identified by cross-referencing the institutional
echocardiographic, ECG and pacing databases, on 1 st
outpatient visit

63. Outcome
Measures
 Primary endpoint was time to heart transplant or death
 Secondary endpoints were overall survival, time to first
heart transplant listing and time to first HF-related
hospitalization
 Longitudinal measures were collected at closest
timepoint to 6 (±3) months post-enrollment, 1 (±0.5)
year, 2 (±0.5) years and 5 (±1) years

64. RESULTS

67.  Median follow-up was 2.7 (0.8-6.1) years overall, and 2.4 (0.6-5.1)
years for non-transplanted survivors
 InitialCRT delivery was transvenous for 17 (27%) patients,
epicardial for 43 (68%) and hybrid for 3 (5%)
 In 19 patients (30%), device capability included defibrillation (CRT-
D).
 Within the control cohort,12 patients (19%) had an implantable
cardioverter defibrillator (ICD) at baseline
 One of the CRT cohort was upgraded to a CRT-defibrillator at 7.4
years post-enrollment, while two controls had ICDs implanted
following enrollment (at 0.4 and 1.3 years post-enrollment).

68. 12 (19%) CRT and 37 (58%) controls reached the primary endpoint of heart transplant or death

74. Control group
 Estimated transplant-free survival was 69%, 57% and
36% at 1,2 and 5 years respectively
 Data from other registries match above findings

75. limitations
 Selection bias
 Too small numbers

76. Conclusions
 In this retrospective study, CRT was associated with a
significantly lower risk of heart transplant or death in
pediatric and/or CHD patients compared to a
propensity score-matched control cohort
 Based on these findings, CRT should be considered for
suitable patients with low systemic ventricle ejection
fraction (<45%), significantly prolonged QRS duration
for age and symptomatic heart failure.