Download Circulation: Heart Failure.2010

Update from the
AHA 2010
Jonathan Silberberg
February 2011
Next week...part 2
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Cardiac hypertrophy
Decompensated heart failure
Brown & Goldstein
PHT in heart failure
LDL cholesterol
Thoracic aorta
Rethinking cardiac hypertrophy
a.
b.
c.
d.
Foetal genes can be good for you!
α1 Gq coupled to foetal gene program
Not downregulated in HF
Negative consequences: ALLHAT /
VeHeFT
e. Α1 induces β myosin in some cells.
Around valves, coronaries
• Paul Simpson. Thomas Smith memorial lecture
Decompensated HF
>10,000 registry
Diuretics the mainstay
8% need CPAP/BiPAP
30% readmission at 30days
Survival f admissions
PHT in heart failure
a.
b.
c.
d.
e.
f.
Redfield et al Mayo clinic
>2000 community echoes
‘HFpEF’ normal systolic function
PCW estimated from E/E’
PA >35mmHg in 80%
PA >48 40% 2-yr mortality (cf 20%)
Treating PHT in HF
a. Semigran Boston
b. 4 trials with endothelin antagonists
negative or adverse
c. PDE5 inhibitors improve exercise
capacity and adaptive changes in
animal models
RELAX trial
Treating PHT in HF
a.
b.
c.
d.
Michelals Edmonton
Work of Srivastata 2006
Embryogenesis: fields of origin
Different transcription factors and
response to load
e. ETRAs depress RV contractility
Treating PHT in HF
a. Lewis Boston
b. Work of Burlaug 2010
c. 2 patterns of CP exercise testing:
a. Plateau due to abnormal RVSW
b. Failure of pulmonary tree to dilate
Exercise Hemodynamics Enhance Diagnosis of Early
Heart Failure With Preserved Ejection FractionBarry A.
Borlaug, MD, Rick A. Nishimura, MD, Paul Sorajja, MD, Carolyn S.P. Lam, MBBS
and Margaret M. Redfield, MD
a. exercise PCWP was used to classify
patients as having HFpEF (PCWP ≥25
mm Hg) or noncardiac dyspnea
b. Exercise-induced elevation in PCWP in
HFpEF was associated with blunted
increases in heart rate, systemic
vasodilation, and cardiac output.
• Circulation: Heart Failure.2010; 3: 588-595
Brown & Goldstein: 1977
a.
b.
c.
d.
e.
Homozygous FH
Cell culture: surface receptor
microassay for HMG-CoA reductase
how do normal cells extract the cholesterol of
LDL? Second messenger?
Purified LDL receptor 1982; cloned human
cDNA; isolated gene1985
Brown & Goldstein: mid-90’s
a.
b.
c.
d.
e.
LDL receptor is regulated
sterol-regulated membrane-bound
transcription factors : SREBPs
Unlike other transcription factors
Synthesized as membrane-bound proteins
attached to the ER
transported to Golgi; processed by proteases;
soluble fragment enters the nucleus
Brown & Goldstein: latest
a.
b.
c.
How is cholesterol transferred from one
organelle to another?
How is the membrane cholesterol content
kept constant?
‘Hydrophobic handover’ involving NiemannPick C (NPC) 1 and 2
2010 thoracic aorta guide
a.
b.
c.
d.
Overall repair at 5.5 cm
Familial or syndrome 4-5 cm
If growth 0.5 cm / year
‘David’ reimplantation 98% survival
• Svensson Cleveland Clinic
Dissection treatment
a. Type A 50% survival at 21 days
b. Ao diameter can be misleading. Half are
‘normal’
c. Standardise imaging! JACC 2010
d. Spurious diameter in C-shape
• Eagle Michigan
Type B: endovascular?
a.
b.
c.
d.
e.
Fattori et al 2006
Endovascular devices for aneurysma
Nonrandomised Circ CV Imaging 2010
Devices for type B;
expect these for type A
• Eagle Michigan
Mr CS
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58 year old man
Atypical chest pain working in kitchen
Raised CK, normal troponin
Abnormal exercise test, negative sestamibi
Normal coronaries
Cold feet, stopped beta blocker
Mr CS
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Grandson neonatal myopathy ?mitochondrial
CK persistently raised
Referred to Hunter Genetics, dna
5 years later: umbilical hernia repair
ECG LVH, hypertension
neurologist: EMG, muscle biopsy, MRI
Type B aortic dissection
Familial Thoracic Aneurysm and
Dissection
a.
There are five genes that are known to cause
FTAAD: ACTA2, responsible for 10-15% of
FTAAD, MYH11 (1%), FBN1 (rare), TGFBR1
(1%), and TGFBR2 (2.5%). Mutations in any
one of these genes cause a predisposition
to develop TAAD to be inherited in a
family.