Chiara Scrocco

Long-term follow-up of patients with short QT syndrome.

OBJECTIVES The aim of this study was to investigate the clinical characteristics and the long-term course of a large cohort of patients with short QT syndrome (SQTS). BACKGROUND SQTS is a rare channelopathy characterized by an increased risk of sudden death. Data on the long-term outcome of SQTS patients are not available. METHODS Fifty-three patients from the European Short QT Registry (75% males; median age: 26 years) were followed up for 64 ± 27 months. RESULTS A familial or personal history of cardiac arrest was present in 89%. Sudden death was the clinical presentation in 32%. The average QTc was 314 ± 23 ms. A mutation in genes related to SQTS was found in 23% of the probands; most of them had a gain of function mutation in HERG (SQTS1). Twenty-four patients received an implantable cardioverter defibrillator, and 12 patients received long-term prophylaxis with hydroquinidine (HQ), which was effective in preventing the induction of ventricular arrhythmias. Patients with a HERG mutation had shorter QTc at baseline and a greater QTc prolongation after treatment with HQ. During follow-up, 2 already symptomatic patients received appropriate implantable cardioverter defibrillator shocks and 1 had syncope. Nonsustained polymorphic ventricular tachycardia was recorded in 3 patients. The event rate was 4.9% per year in the patients without antiarrhythmic therapy. No arrhythmic events occurred in patients receiving HQ. CONCLUSIONS SQTS carries a high risk of sudden death in all age groups. Symptomatic patients have a high risk of recurrent arrhythmic events. HQ is effective in preventing ventricular tachyarrhythmia induction and arrhythmic events during long-term follow-up.

New echocardiographic insights in short QT syndrome: More than a channelopathy?

BACKGROUND Short QT syndrome (SQTS) is a congenital ion channel disease characterized by an increased risk of sudden cardiac death. Little is known about the possibility that accelerated repolarization alters mechanical function in SQTS. OBJECTIVES The study investigated the presence of left ventricular dysfunction and mechanical dispersion, assessed by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), and their correlation with QT interval duration and genetics. METHODS Fifteen SQTS patients (7 with HERG and 3 with KCNQ1 mutation) were studied. Electrocardiographic and echocardiographic parameters were compared with age- and sex-matched healthy controls. RESULTS When compared to the control group, SQTS patients showed reduced left ventricular contraction (global longitudinal strain: -16.0% ± 3.4% vs -22.6% ± 1.7%, P < .001; myocardial performance index 0.59 ± 0.17 vs 0.34 ± 0.08, P < .001) and a higher incidence of ejection fraction <55% (odds ratio 11, 95% confidence interval 1.045-374, P = .04). Mechanical dispersion assessed by TDI (P < .01) and STE (P < .001) was higher in the SQTS group than in controls; each parameter showed a significant inverse correlation with QT interval but not with QT dispersion. CONCLUSION This study showed that in SQTS systolic function may also be affected. SQTS patients presented a significant dispersion of myocardial contraction. TDI and STE could become part of the evaluation of this rare disease.

PQ segment depression in patients with short QT syndrome: A novel marker for diagnosing short QT syndrome?

BACKGROUND Patients with short QT syndrome (SQTS) have an increased risk for atrial tachyarrhythmias, ventricular tachyarrhythmias, and/or sudden cardiac death. PQ segment depression (PQD) is related to atrial fibrillation and carries a poor prognosis in the setting of acute inferior myocardial infarction and is a well-defined electrocardiographic (ECG) marker of acute pericarditis. OBJECTIVE To evaluate the prevalence of PQD in SQTS and to analyze the association with atrial arrhythmias. METHODS Digitalized 12-lead ECGs of SQTS patients were evaluated for PQD in all leads and for QT intervals in leads II and V5. PQD was defined as ≥0.05 mV (0.5 mm) depression from the isoelectric line. RESULTS A total of 760 leads from 64 SQTS patients (mean age 36 ± 18 years; 48 [75%] men) were analyzed. PQD was seen in 265 (35%) leads from 52 (81%) patients and was more frequent in leads II, V3, aVF, V4, and I (n = 43 [67%], n = 30 [47%], n = 27 [42%], n = 25 [39%], and n = 25 [39%], respectively). Nine of 64 (14%) patients presented with atrial tachyarrhythmias, and all of them had PQD. CONCLUSION Fifty-two of 64 (81%) patients with SQTS reveal PQD. As PQD is rarely observed in healthy individuals, this ECG stigma may constitute a novel marker for SQTS in addition to a short QT interval.

Usefulness of exercise test in the diagnosis of short QT syndrome

AIMS Short QT syndrome (SQTS) is a rare arrhythmogenic inherited heart disease. Diagnosis can be challenging in subjects with slightly shortened QT interval at electrocardiogram. In this study we compared the QT interval behaviour during exercise in a cohort of SQTS patients with a control group, to evaluate the usefulness of exercise test in the diagnosis of SQTS. METHODS AND RESULTS Twenty-one SQTS patients and 20 matched control subjects underwent an exercise test. QT interval was measured at different heart rates (HRs), at rest and during effort. The relation between QT interval and HR was evaluated by linear regression analysis according to the formula: QT = β ×HR + α, where β is the slope of the linear relation, and α is the intercept. Rest and peak exercise HRs were not different in the two groups. Short QT syndrome patients showed lower QT intervals as compared with controls both at rest (276 ± 27 ms vs. 364 ± 25 ms, P < 0.0001) and at peak exercise (228 ± 27 ms vs. 245 ± 26 ms, P = 0.05), with a mean variation from rest to peak effort of 48 ± 14 ms vs. 120 ± 20 ms (P < 0.0001). Regression analysis of QT/HR relationship revealed a less steep slope for SQTS patients compared with the control group, never exceeding the value of -0.90 ms/beat/min (mean value -0.53 ± 0.15 ms/beat/min vs. -1.29 ± 0.30 ms/beat/min, P < 0.0001). CONCLUSION Short QT syndrome patients show a reduced adaptation of the QT interval to HR. Exercise test can be a useful tool in the diagnosis of SQTS.

Etiological diagnosis, prognostic significance and role of electrophysiological study in patients with Brugada ECG and syncope ☆

BACKGROUND Syncope is considered a risk factor for life-threatening arrhythmias in Brugada patients. Distinguishing a benign syncope from one due to ventricular arrhythmias is often difficult, unless an ECG is recorded during the episode. Aim of the study was to analyze the characteristics of syncopal episodes in a large population of Brugada patients and evaluate the role of electrophysiological study (EPS) and the prognosis in the different subgroups. METHODS AND RESULTS One hundred ninety-five Brugada patients with history of syncope were considered. Syncope were classified as neurally mediated (group 1, 61%) or unexplained (group 2, 39%) on the basis of personal and family history, clinical features, triggers, situations, associated signs, concomitant therapy. Most patients underwent EPS; they received ICD or implantable loop-recorder on the basis of the result of investigations and physicians judgment. At 62±45months of mean follow-up, group 1 showed a significantly lower incidence of arrhythmic events (2%) as compared to group 2 (9%, p<0.001). Group 2 patients with positive EPS showed the highest risk of arrhythmic events (27%). No ventricular events occurred in subjects with negative EPS. CONCLUSION Etiological definition of syncope in Brugada patients is important, as it allows identifying two groups with different outcome. Patients with unexplained syncope and ventricular fibrillation induced at EPS have the highest risk of arrhythmic events. Patients presenting with neurally mediated syncope showed a prognosis similar to that of the asymptomatic and the role of EPS in this group is unproven.

The lack of effect of sotalol in short QT syndrome patients carrying the T618I mutation in the KCNH2 gene

Carla Giustetto, MD, Chiara Scrocco, MD, Daniela Giachino, MD, PhD, Claudio Rapezzi, MD, Barbara Mognetti, PhD, Fiorenzo Gaita, MD From the Division of Cardiology, University of Torino, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Torino, Italy, Medical Genetics, University of Torino, Department of Clinical and Biological Sciences, Torino, Italy, Medical Genetics San Luigi University Hospital, Orbassano, Italy, Institute of Cardiology, University of Bologna, and S. Orsola-Malpighi Hospital, Bologna, Italy, and Pharmacology Unit, University of Torino, Department of Clinical and Biological Sciences, Torino, Italy.

Shortening of the Short Refractory Periods in Short QT Syndrome

Background Diagnosis of short QT syndrome (SQTS) remains difficult in case of borderline QT values as often found in normal populations. Whether some shortening of refractory periods (RP) may help in differentiating SQTS from normal subjects is unknown. Methods and Results Atrial and right ventricular RP at the apex and right ventricular outflow tract as determined during standard electrophysiological study were compared between 16 SQTS patients (QTc 324±24 ms) and 15 controls with similar clinical characteristics (QTc 417±32 ms). Atrial RP were significantly shorter in SQTS compared with controls at 600‐ and 500‐ms basic cycle lengths. Baseline ventricular RP were significantly shorter in SQTS patients than in controls, both at the apex and right ventricular outflow tract and for any cycle length. Differences remained significant for RP of any subsequent extrastimulus at any cycle length and any pacing site. A cut‐off value of baseline RP <200 ms at the right ventricular outflow tract either at 600‐ or 500‐ms cycle length had a sensitivity of 86% and a specificity of 100% for the diagnosis of SQTS. Conclusions Patients with SQTS have shorter ventricular RP than controls, both at baseline during various cycle lengths and after premature extrastimuli. A cut‐off value of 200 ms at the right ventricular outflow tract during 600‐ and 500‐ms basic cycle length may help in detecting true SQTS from normal subjects with borderline QT values.

Reply to the Editor--PQ-segment depression in short QT syndrome patients: a novel marker for diagnosing short QT syndrome?

The comments of Dr Chhabra and colleagues regarding the dynamic variability of PQ-segment depression (PQD) and the timing of the electrocardiograms (ECGs) are appreciated. In acute pericarditis, the PQ segment reflects the evolving pathophysiology of the disease and it changes accordingly. Although the exact mechanism of PQD in short QT syndrome (SQTS) is not known, one should not expect a major variability in PQD because the pathology remains unchanged in these patients. This assertion is also concordant with our observation that PQD persists with only slight deviations during follow-up. Nevertheless, the retrospective nature of the study does not allow us to accept this observation as a solid “finding.” Another concern pointed out by Dr Chhabra and colleagues was the timing of the ECG tracings. The ECG tracings were from patients diagnosed with SQTS (from the European SQTS registry), and none of the ECG tracings used for the analysis were taken from the immediate post-resuscitation phase. Furthermore, patients were free from antiarrhythmic drugs that may affect cardiac action potentials and thus possibly the PQ segment. Cardiac arrest secondary to myocardial infarction may also cause PQD owing to pericarditis during acute myocardial infarction or post-resuscitation. However, cardiac arrest occurred in SQTS in the absence of acute ischemia (STelevation myocardial infarction and non-ST-elevation myocardial infarction were ruled out). Another concern raised by the authors was regarding the analysis of PQD in patients with atrial fibrillation/flutter. As correctly pointed out by Dr Chhabra and colleagues, the analysis of the PQ segment is possible only in sinus rhythm. All the patients who developed atrial fibrillation—either paroxysmal, persistent, or permanent—had at least 1 ECG with sinus rhythm, enabling the analysis of PQD in these patients. In general, we also agree that further studies are needed to better understand the underlying mechanism and clinical significance of PQD in SQTS.