Author Interviews, Heart Disease, JACC / 08.08.2016
Newly Diagnosed Brugada Syndrome Have a Different Prognosis
MedicalResearch.com Interview with:
Ruben Casado-Arroyo, MD, PhD
Heart Rhythm Management Center
Cardiovascular Division, UZ Brussel–Vrije Universiteit Brussel,
Cardiology Department, Arrhythmia Section
Erasmus Hospital, Université Libre de Bruxelles
Brussels, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The objective of this study is to evaluate the evolution of the
presentation of Brugada Syndrome (BrS) during the last 30 years. Only
the first diagnosed patient of each family was included. The database
was divided in two periods (early and latter group) in relation to the
consensus conference of 2002.
Aborted sudden death as the first manifestation of the disease
occurred most frequently in the earlier period 12.1% versus 4.6% of
the latter group. Inducibility (induction of ventricular fibrillation)
during programmed electrical stimulation was achieved in 34.4%
(earlier) and 19.2% (latter) of patients, respectively. A spontaneous
type 1 electrocardiogram pattern that is a coved type ST elevation
with at least 2 mm (0.2 mV) J-point elevation a gradually descending
ST segment followed by a negative T-wave was presented at diagnosis
50.3% (earlier) versus 26.2% (latter patients). Early group patients
had a higher probability of a recurrent arrhythmia (sudden cardiac
death or ventricular arrhythmias) during follow-up (19%) than those
of the latter group (5%). All these difference were significative.
Overall, the predictors of recurrent arrhythmias were previous sudden
cardiac death and inducibility. In the latter period, only previous
sudden cardiac death was a predictor of arrhythmic events.























Dr. Audrey Chang[/caption]
MedicalResearch.com Interview with:
Dr. Audrey Chang, PhD
Kamm-Stull Lab
UT Southwestern Medical Center
AudreyN.Chang@UTSouthwestern.edu
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The heart is a singular kind of muscle that contracts and relaxes continuously over a lifetime to pump blood to the body’s organs. Contractions depend on a motor protein myosin pulling on actin filaments in specialized structures. Heart contraction is improved when myosin has a phosphate molecule attached to it (phosphorylation), and a constant amount of phosphorylation is essential for normal heart function. The amount of phosphorylation necessary for optimal cardiac performance is maintained by a balance in the activities of myosin kinase enzymes that add the phosphate and an opposing phosphatase enzyme that removes the phosphate. If the amount of phosphorylation is too low, heart failure results. Animal models with increased myosin phosphorylation have enhanced cardiac performance that resist stresses that cause heart failure.
In this recent study reported in PNAS, a new kinase that phosphorylates myosin in heart muscle, MLCK4, was discovered and its crystal structure reported, a first for any myosin kinase family member. Compared to distinct myosin kinases in other kinds of muscles (skeletal and smooth), this cardiac-specific kinase lacks a conserved regulatory segment that inhibits kinase activity consistent with biochemical studies that it is always turned on. Additionally, another related myosin kinase found only in heart muscle (MLCK3) contains a modified regulatory segment, allowing partial activity enhanced by the calcium modulator protein, calmodulin. Thus, both myosin kinases unique to cardiac muscle provide phosphate to myosin in normal beating hearts to optimize performance and prevent heart failure induced by stresses.
