Find information on thousands of medical conditions and prescription drugs.

Long QT syndrome type 2

The long QT syndrome (LQTS) is a heart disease in which there is an abnormally long delay between the electrical excitation (or depolarization) and relaxation (repolarization) of the ventricles of the heart. It is associated with syncope (loss of consciousness) and with sudden death due to ventricular arrhythmias. Arrhythmias in individuals with LQTS are often associated with exercise or excitement. The cause of sudden cardiac death in individuals with LQTS is ventricular fibrillation. more...

Home
Diseases
A
B
C
D
E
F
G
H
I
J
K
L
Amyotrophic lateral...
Bardet-Biedl syndrome
Labyrinthitis
Lafora disease
Landau-Kleffner syndrome
Langer-Giedion syndrome
Laryngeal papillomatosis
Laryngomalacia
Lassa fever
LCHAD deficiency
Leber optic atrophy
Ledderhose disease
Legg-Calvé-Perthes syndrome
Legionellosis
Legionnaire's disease
Leiomyoma
Leiomyosarcoma
Leishmaniasis
Lemierre's syndrome
Lennox-Gastaut syndrome
Leprechaunism
Leprophobia
Leprosy
Leptospirosis
Lesch-Nyhan syndrome
Leukemia
Leukocyte adhesion...
Leukodystrophy
Leukomalacia
Leukoplakia
LGS
Li-Fraumeni syndrome
Lichen planus
Ligyrophobia
Limb-girdle muscular...
Limnophobia
Linonophobia
Lipodystrophy
Lipoid congenital adrenal...
Liposarcoma
Lissencephaly
Lissencephaly syndrome...
Listeriosis
Liticaphobia
Liver cirrhosis
Lobster hand
Locked-In syndrome
Loiasis
Long QT Syndrome
Long QT syndrome type 1
Long QT syndrome type 2
Long QT syndrome type 3
LSA
Lung cancer
Lupus erythematosus
Lyell's syndrome
Lygophobia
Lyme disease
Lymphangioleiomyomatosis
Lymphedema
Lymphoma
Lymphosarcoma
Lysinuric protein...
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
Medicines

Individuals with LQTS have a prolongation of the QT interval on the ECG. The Q point on the ECG corresponds to the beginning of ventricular depolarization while the T point corresponds to the beginning of ventricular repolarization. The QT interval is measured from the Q point to the end of the T wave. While many individuals with LQTS have persistent prolongation of the QT interval, some individuals do not always show the QT prolongation; in these individuals, the QT interval may prolong with the administration of certain medications.

Genetics

The two most common types of LQTS are genetic and drug-induced. Genetic LQTS can arise from mutation to one of several genes. These mutations tend to prolong the duration of the ventricular action potential (APD), thus lengthening the QT interval. LQTS can be inherited in an autosomal dominant or an autosomal recessive fashion. The autosomal recessive forms of LQTS tend to have a more severe phenotype, with some variants having associated syndactyly or congenital neural deafness. A number of specific genes loci have been identified that are associated with LQTS. Following is a list of the most common mutations:

  • LQT1 - mutations to the alpha subunit of the slow delayed rectifier potassium channel (KvLQT1 or KCNQ1). The current through the heteromeric channel (KvLQT1+minK) is known as IKs. This mutation is thought to cause LQT by reducing the amount of repolarizing action potential current that prolongs action potential duration (APD). These mutations tend to be the most common yet least severe.
  • LQT2 - mutations to the alpha subunit of the fast delayed rectifier potassium channel (HERG + miRP). Current through this channel is known as IKr. This phenotype is also probably caused by a reduction in repolarizing current.
  • LQT3 - mutations to the alpha subunit of the sodium channel (SCN5A). Current through is channel is commonly referred to as INa. Depolarizing current through the channel late in the action potential is thought to prolong APD. The late current is due to failure of the channel to remain inactivated and hence enter a bursting mode in which significant current can enter when it should not. These mutations are more lethal but less common.
  • LQT4 - mutations in an anchor protein Ankyrin B which anchors the ion channels in the cell. Very rare.
  • LQT5 - mutations in the beta subunit MinK which coassembles with KvLQT1.
  • LQT6 - mutations in the beta subunit MiRP1 which coassembles with HERG.
  • LQT7 - mutations in the potassium channel KCNJ2 which leads to Andersen-Tawil syndrome.
  • LQT8 - mutations in the calcium channel Cav1.2 encoded by the gene CACNA1c leading to Timothy's syndrome

Other mutations affect the beta subunits ion channels. For example LQT6 affects minK (aka KCNE1) which is the beta subunit that coassembles with KCNQ1 to form IKs channels.

Read more at Wikipedia.org


[List your site here Free!]


Weight loss sustainable with rimonabant, 2-year results show
From OB/GYN News, 4/15/05 by Bruce Jancin

ORLANDO, FLA. -- The outstanding weight loss and cardiovascular-risk reduction previously reported after 1 year of rimonabant therapy were maintained after 2 years of treatment in the phase III Rimonabant in Obesity-Europe trial, Luc Van Gaal, M.D., reported at the annual meeting of the American College of Cardiology.

The safety and tolerability profiles of rimonabant, first in a new class of selective endocannabinoid type 1-receptor blockers, also remained reassuring after 2 years' treatment, added Dr. Van Gaal, professor of diabetology, metabolism, and clinical nutrition at the University of Antwerp (Belgium) and principal investigator for Rimonabant in Obesity (RIO)-Europe.

The new 2-year study results are virtually superimposable on the 2-year outcomes of the phase III RIO-North America trial presented last fall at the annual scientific sessions of the American Heart Association (OB.GYN. NEWS, Jan. 1, 2005, p. 36).

Armed with data from more than 6,600 overweight and obese participants in these two trials plus two Sanofi-Aventis-sponsored 1-year phase III trials, the company plans to file before midyear for Food and Drug Administration and European Commission approval of rimonabant 20 mg/day for weight loss, a spokesman told this newspaper. Simultaneously, Sanofi-Aventis will file for a smoking cessation indication, the subject of another extensive phase III rimonabant clinical trials program.

RIO-Europe was a randomized, double-blind, placebo-controlled study involving 1,507 overweight or obese patients with a mean baseline body mass index of 37 kg/[m.sup.2] and a mean age of 45 years. As is typical in weight loss trials, 80% were women. Participants were strongly encouraged by dietitians and counselors to adopt a 600-kcal/day-deficit diet and increase their physical activity.

In RIO-Europe, 20 mg/day of rimonabant resulted in a mean 7.2-kg weight loss among those who completed 2 years of treatment, compared with a mean 2.5-kg loss in those on placebo. In an intent-to-treat analysis, the mean weight loss was 5.5 kg in the rimonabant arm and 1.2 kg with placebo.

At baseline, more than 42% of study participants met National Cholesterol Education Program criteria for metabolic syndrome. After 2 years on rimonabant 20 mg/day, the prevalence of metabolic syndrome fell by 57%, compared with a 34% drop with placebo.

Mean waist circumference--a measure of intraabdominal obesity--was reduced by 7.5 cm after 2 years on rimonabant, from a baseline of 110 cm, and by 3.4 cm in the placebo group.

More than 32% of patients who completed 2 years of rimonabant treatment lost at least 10% of their baseline body weight--a medically meaningful threshold--as compared with 11% on placebo.

HDL-cholesterol levels climbed by 28.2%, compared with 16.8% with placebo. Triglycerides fell by an average of 8.8% with rimonabant while rising 6.3% in the placebo group.

Rimonabant also significantly improved insulin sensitivity. Only about half of the observed improvement in lipids could be explained by the weight loss, implying that rimonabant exerts direct metabolic effects beyond weight loss, Dr. Van Gaal continued.

As was the case after 1 year, rimonabant resulted in no significant changes in heart rate, blood pressure, or QT interval at the 2-year mark. The most common treatment side effects were nausea and other GI symptoms and dizziness, all of which were more frequent in year 1 and mostly mild.

Discussant Julius M. Gardin, M.D., called RIO-Europe "a remarkable study--really a landmark study in the field of obesity."

He singled out the 57% decrease in prevalence of metabolic syndrome as particularly impressive in terms of future likely cases of cardiovascular disease and diabetes prevented. He also called the 2-year safety data "heartening."

But he sounded a note of caution: "If you look at the weight-loss data, at 2 years the curves are starting to head upward. And we all know that obesity is not just a 2-year problem.... We'd really like to know what happens after 2 years. We'll want to see postmarketing studies to see if this effect is maintained long-term."

Dr. Gardin also raised several philosophical issues that have been on the minds of many physicians who endured the litigious frenzy that followed the fen-phen (fenfluramine-phentermine) controversy.

"Hypothetically, what if rimonabant is approved, hits the market, we have 5 million prescriptions out there, and we get all of the wonderful positive effects described in the study--but it turns out one person per million dies related to the drug? What should reasonable people do about this? Should they say that's an acceptable risk-benefit ratio? Or should we handle it the way previous anorexigens were handled, with punitive measures? And who makes this decision?" asked Dr. Gardin, chief of cardiology at St. John Hospital and Medical Center, Detroit.

Another big societal issue is whether rimonabant therapy should be considered in anyone who meets a defined body mass index criterion, or if additional risk factors, such as the metabolic syndrome, ought to be required.

"I would hate to see prescription of a medication subvert efforts being made by the public health community to encourage prudent eating, reduction of calories, exercise, and other healthful lifestyle measures," Dr. Gardin cautioned.

BY BRUCE JANCIN

Denver Bureau

COPYRIGHT 2005 International Medical News Group
COPYRIGHT 2005 Gale Group

Return to Long QT syndrome type 2
Home Contact Resources Exchange Links ebay