Dust, cat hair, pollen

None

The recorded ECG (Fig. 25.2a, b) revealed sinus rhythm with 58 bpm heart rate, normal atrioventricular and intraventricular conduction, and normal ventricular repolarization with a corrected QT interval 600 ms long.

A complete echocardiographic examination was performed and showed normal dimensions and function of cardiac chambers, a mild prolapse of the posterior mitral leaflet with trace of mitral regurgitation, and a mild tricuspid regurgitation with normal pulmonary artery systolic pressure.

No reversible cause of QT interval prolongation was found.

All the family members underwent ECG evaluation, and either the father or brother showed a prolonged QT interval. They both were not taking any medications which could alter the QT interval, and laboratory findings did not show electrolyte abnormalities.

These findings altogether were suggestive for hereditary long QT syndrome. Genetic assessments were therefore performed and it is still underway.

Hereditary long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval detectable on the standard 12-lead ECG with or without T wave [1]. These abnormalities of ventricular repolarization can be present in other family members of the affected subject.

The natural history of LQTS is characterized by the development of life-threatening ventricular arrhythmias such as torsade de pointes (TdP). This arrhythmia can be self-limiting and asymptomatic or they can manifest with syncope or sudden cardiac death (SCD) [2].

The prevalence of this genetic disorder is estimated to be at least 1:5,000 subjects. Considering that the affected subject can be asymptomatic and there are cases of sudden cardiac death with no defined etiology, the real prevalence of LQTS may be considerably higher [1, 2].

Moreover, 10–40 % of affected patients present a nondiagnostic QT interval at rest because of an intermittent nature of the ECG abnormalities or a borderline QT value that make the diagnosis challenging [3].

Long QT syndrome more often manifests before puberty in males and after puberty in females, and the probability of a cardiac event depends on the degree of QT prolongation.

Among untreated symptomatic patients, mortality is high, with 20 % of deaths in the first year after the first cardiac event and approximately 50 % within 10 years [2].

Since the discovery of the first LQTS-responsible genes in 1990s, a lot more genes have been related to the syndrome and more than 500 mutations are described nowadays, resulting in 10 different phenotypes (LQTS 1–10).

In about 75 % of patients, mutations involve three main causative genes:

Nearly 70 % of all LQTS are secondary to loss-of-function mutations involving IKs (30–35 %) or IKr (25–40 %) potassium channels, while approximately 5 % result in a gain-of-function mutation involving sodium channel. Less frequently, patients with congenital LQTS present mutation involving:

In addition, 15–20 % of affected patients present a negative genetic assessment.

The majority of LQTS is inherited as an autosomal dominant trait: the Romano-Ward syndrome affects 1 per 5,000 persons. Sporadic (or de novo) alterations occur 5–10 % of the time. The autosomal recessive form of LQTS, also known as Jervell and Lange-Nielsen syndrome, was firstly described in 1957. It probably affects less than 1 per million people and results from complete loss of Kv7.1 channel function, which precipitates sensorineural deafness in addition to LQT1 or LQT5 mutation [2, 4].

The three main genotypes (LQT1, LQT2, and LQT3) present distinctive clinical phenotypes with important implications in diagnosis, treatment, and long-term clinical course. Indeed, the recognition of gene-specific features can be used to choose the most suitable therapy and to give the correct recommendations to probands and their family. The gene-specific phenotypes include different triggers of ventricular arrhythmias, different ages of symptom onset, and specific ECG morphologies [2, 4].

Patients with LQT1 and less part of LQT2 patients usually present the greater risk of cardiac events after triggers associated with adrenergic stimulation [5]. Life-threatening arrhythmias have been shown to occur under specific circumstances: while diving and swimming for LQT1 patients or acoustic stimuli (such as alarm clock ringing) or sudden awakening for LQT2 patients [4, 6–8].

On the other hand, LQT3 is characterized by the higher risk of events at rest or during sleep.

Patients with LQT3 have fewer events during exercise or stress because they significantly shorten their QTc at high frequencies and therefore they become less susceptible to catecholamine-induced arrhythmias [9]. These findings have consistent clinical implications and explain why these patients have less or no benefit at all from beta-blocker therapy.

Age of first manifestations varies from one genotype to another. In fact, generally, the age of first events is lower in LQT1 than in LQT2 and LQT3 [4].

Some differences can be noticed on the standard 12-lead ECG too. Each one of the three major genotypes (LQT1 to LQT3) seems to have a distinctive T-wave repolarization pattern on the ECG, as shown in Fig. 25.3.

Moreover, every genotype has a different response to exercise. LQT1 patients fail to appropriately shorten their QT interval during exercise and QTc may further lengthen. This effect is due to IKs that in normal subjects is responsible for the abbreviation of the action potential at higher heart rates. On the contrary, patients with LQT3 show shortening of QT interval during exercise. In LQT2, QTc duration behavior is variable [4].

Finally, LQT1 patients have a peculiar response to epinephrine. Epinephrine infusion has an excellent performance in the detection of LQTS1 because it provokes a significant and stable prolongation of the QTc in these patients [10, 12].

Table 25.1 shows the characteristics of different genotypes of LQTS.

The long QT syndrome’s main manifestations are electrocardiographic anomalies, syncope, cardiac arrest, and sudden cardiac death.

The ECG anomalies are very different and they depend in part on the type of QT syndrome. The main alteration is the prolongation of the QT interval, but is not always present at rest. In a certain percentage of patients, the QT interval can even be normal (10 % in LQT3 and 37 % in LQT1) [12]. In these cases, the QT interval’s prolongation can be evident during exercise test or infusion of epinephrine [4, 9–11]. Furthermore, repolarization can have strange aspects. For example, notches on the T wave are typical of LQT2.

Syncope, cardiac arrest, and sudden death are the result of ventricular arrhythmias due to the arrhythmogenic condition strictly linked to the genetic and electrical disorders of the disease. These arrhythmias are most of all torsade de pointes VT that become clinically manifest depending on their duration. Sudden death occurs when the arrhythmia is not self-limiting and degenerates into ventricular fibrillation.

In many cases, the diagnosis of LQTS can easily be done with a standard 12-lead ECG at rest, measuring the QT interval and correcting it with Bazett’s formula (QTc = QT (ms)/√RR(s)). However, there are hidden cases of LQTS in which the QT interval can be normal or borderline at rest (about 20–25 %) [12–16].

Some useful tests have been proposed to unmask the concealed forms of LQTS, and ongoing clinical trials are evaluating and validating them. These tests are:

Stay updated, free articles. Join our Telegram channel

Join