4 congresso nazionale sulla medicina di genere … › 20171127 › leoni.pdf · le aritmie...

University of Padova

Dott.ssa Loira LeoniClinica Cardiologica Università di Padova

Responsabile Aritmologia Pediatrica e del Cardiopatico CongenitoCo-Chairman Area pediatrica AIAC

4° CONGRESSO NAZIONALE SULLA MEDICINA DI GENERE

[email protected]@aopd.veneto.it

“CARDIOLOGIA E ONCOLOGIA GENERE-SPECIFICHE”

Le aritmie cardiache

PADOVA 27-28 NOVEMBRE 2017


LE ARITMIE CARDIACHE GENERE-SPECIFICHE


Henry C. Bazett An analysis of the time-relations of electrocardiograms.

Heart 1920; 7: 353–370




PUBERTA’




Summary of gender differences in electrophysiologic properties and ECG




Summary of gender differences in Clinical arrhythmias


Hormonal effects on the expression or function of ion channels

And/or differences in autonomic tone:

• greater sympathetic activity and a lower baroreflexresponse in men

• more pronounced parasympathetic or vagal activity in women

Two principle mechanisms have been proposed to explain the differences between

the sexes differential




Genomic effect 17β- oestradiol

Non genomic effect testosterone and progesterone17β- oestradiol

HORMONAL EFFECT

The gender differences in fundamental cardiac electrophysiology result from

variable ion channel expression and diverse sex hormonal regulation via

long term genomic and acute non-genomic pathways



prolonged cardiac action potential duration

shortened the early part of repolarization


Heart rateWomen have higher heart rates than men (+ 3-5

beats)

Intrinsic difference in the

sinus node



Mechanisms:-direct or indirect hormonal effects on the electrical properties of the sinus node-differences in stroke volume-differences in autonomic influences on the sinus node


Women have longer corrected QT (QTc) intervals than men

Male and female schoolchildren have similar QTc intervals

At the time of puberty, the average male QTc interval shortens

As men age, the QTc interval gradually increases over time but never reaches the duration of the QTc interval in women

QT intervalFormula di Bazett’s

•QTc max: 450 ms460 ms

The gender differences in QTc intervals suggest that gender hormones are

responsible:EFFECT OF FEMALE HORMONES ON CA++

AND K+ CHANNEL FUNCTION AND ON THE FAST AND PERSISTENT SODIUM CURRENT

AND SODIUM-CALCIUM EXCHANGE



SPERIMENTAL DATA

17β- oestradiol induced prolongation of action potential duration (APD) and QTc interval

Progesterone and testosterone inducing shortening of APD.




prolonged cardiac action potential duration

shortened cardiac action potential

duration

http://upload.wikimedia.org/wikipedia/commons/3/33/Ciclo_mestruale.png



Voltage and Duration of the P and QRS Complex

In women, a shorter QRS complex and a smaller QRS voltage have been reported

A shorter P wave duration and PR interval have also been reported in women

When the QRS interval gets shorter (QRS<80 ms), repolarization differences between the genders disappear






Specific Arrhythmias


Supraventricular tachycardia (AVNRT)

Atrioventricular nodal reentrant tachycardia

Women predominance (2:1)Evidence of hormonal effects on the

triggers and timing of SVTs:More SVT episodes and symptomatic

episodes during the luteal phase of the menstrual cycle, when progesterone levels are elevated

cyclical variation in SVT inducibility: not inducibility during electrophysiologic studies performed at midcycle; and inducibility during menstruation.






More often in women than men, < 40 yearsSyndrome in which there is a high heart rate at rest

as well as an exaggerated heart rate response to stress

Abnormal autonomic regulation of the sinus node

There is a possibility that this disease could be related to an immunologic disorder involving cardiac-adrenergic receptors

[email protected]



Inappropriate sinus tachycardia


Atrial Fibrillation

Men have a 1.5-fold higher risk for developing AF compared with women

The prevalence of AF increases in men with increasing age but does not change in women

The absolute number of women with AF is greater than that of men in older age groups because of the overall greater longevity of women




Male rodent pulmonary vein myocytes have greater spontaneous beating rates, more burst firing, and larger isoproterenol- induced delayed after depolarizations

Male left atrial cardiomyocytes also have greater late Na+ current and Ca2+ content, which may explain larger delayed afterdepolarizations and more frequent triggered activity.



There are sex differences in atrial electrophysiology and AF


Differences in outcomes and prognosisThe 2 genders were prescribed anticoagulation at

similar rates. At 1 year, women did have a significantly higher rate of stroke (2.2% vs 1.2%, p 0.011) and major bleeding events (2.2% vs 1.3%, p 0.028)

The greater risk for QT prolongation and Torsades de Pointes in women compared with men must be recognized when choosing to prescribe antiarrhythmic drugs.



Atrial Fibrillation


Female gender has to be considered as an independent risk factor when making decisions regarding anticoagulation treatment in patients with AF, in concordance with European Society of Cardiology guidelines




Differences in outcomes and prognosis

Women with AF are more likely than men to have embolic strokes.

Symptoms of AF also appear more frequently in women: higher mean heart rates and longer episodes.

Women with AF were older, had lower quality of life, had more significant comorbidities, and had more symptoms compared with men

Women were treated less aggressively, with fewer cardioversions and catheter ablations




There is a lower number of women undergoing catheter ablation

Females have longer history of AF before being considered for ablation, which may have resulted in increased electrical and structural remodeling; this may explain the lower success rate of ablation.

Females fail more catheter ablations for long-standing persistent AF. However, taking reablation cases into account, women have a similar overall success rate to men, and in fact women underwent a second ablation more frequently than men.




CHANELLOPATHY AND SUDDEN DEATH




Congenital LQTSFemale prevalence

Male subjects are at higher risk for cardiac events (syncope, cardiac arrest, or SCD) before puberty and women are at higher risk during adulthood

The first events in men were more often fatal compared with women

The difference in the timing of events is likely related to the shortening of QT intervals in male subjects after puberty

This unbalanced gender distribution cannot be accounted for by genetic transmission, because the inheritance pattern is not gender linked




Acquired LQTS

Usually seen with electrolyte abnormalities or the use of medications that prolong ventricular repolarization

Women are more likely to develop Torsades de Pointes from antiarrhythmic medications, such as type IA (quinidine, procainamide, and disopyramide) and type III (sotalol, dofetilide, ibutilide, and amiodarone) drugs





Brugada Syndrome

The male-predominant risk of Brugada syndrome is so apparent that, in some southeastern Asian villages, young men dress in women’s clothes to deceive evil spirits from taking their lives during sleep.

Male individuals with Brugada syndrome have a higher rate of spontaneous type 1 electrocardiographic pattern and are more likely to experience VF or sudden cardiac death (SCD) during follow-up.



Sudden Cardiac DeathEpidemiologic studies evaluating out-of-hospital cardiac arrests

demonstrate that women present more commonly with asystole and pulseless electrical activity, whereas men usually have ventricular tachycardia and ventricular fibrillation

Women had a significantly lower incidence of SCD in all age groups (1/2 that of men)

Women also exhibited a 10- to 20-year delay in SCD event rates compared with men

Ten percent of the women have structurally normal hearts, whereas 3% of the men

[email protected]




Sudden Cardiac DeathThose women with known coronary artery disease experienced

SCD at 1/4 the rate of men.

Survivors of SCD found a much higher percentage of men with coronary artery disease than women (80% vs 45%)

Women had an equal risk for arrhythmic versus nonarrhythmic deaths until 1 year after myocardial infarction, whereas men had a larger risk for arrhythmic death over the same time frame

Implantable cardioverterdefibrillator therapy should be considered in all appropriate patients: cardioverterdefibrillators appear to be safe and efficacious therapy regardless of gender

Rates of implantable

cardioverterdefibrillator implantation for women appear to lag behind those

of men



University of [email protected]




Aritmologia Pediatrica Padova



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