Artemisia Theopistou

Arrhythmogenic right ventricular cardiomyopathy/dysplasia on the basis of the revised diagnostic criteria in affected families with desmosomal mutations

Aims To evaluate arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) in affected families with desmosome mutations on the basis of the recently revised Task Force Criteria (TFC). Methods and results One hundred and three consecutive carriers of pathogenic desmosome mutations and 102 mutation-negative relatives belonging to 22 families with dominant and 14 families with recessive ARVC/D were evaluated according to the original and revised TFC. Serial cardiac assessment with 12-lead, signal-averaged, and 24 h ambulatory ECG and two-dimensional echocardiography was performed. Clinical events and outcome were prospectively analysed up to 24 years (median 4 years). With the revised criteria, 16 carriers were newly diagnosed on the basis of ECG abnormalities in 100%, ventricular arrhythmias in 79%, and functional/structural alterations in 31%, increasing diagnostic sensitivity from 57 to 71% (P = 0.001). Task Force Criteria specificity improved from 92 to 99% (P = 0.016). In dominant mutation carriers, penetrance changed significantly (61 vs. 42%, P = 0.001); no changes were observed in recessive homozygous carriers (97 vs. 97%, P = 1.00). Affected carriers according to the revised TFC (n = 73) had 12-lead ECG abnormalities in 96%, ventricular arrhythmias in 91%, and functional/structural alterations fulfilling echocardiographic criteria in 76%. Cumulative and event-free survival did not differ significantly between dominant and recessive affected carriers, being at 78.6 vs. 76 and 51.7 vs. 55.4%, respectively, by the age of 40 years. Conclusion Revised TFC increased diagnostic sensitivity particularly in dominant ARVC/D. Serial family evaluation may rely on electrocardiography which seems to have the best diagnostic utility particularly in early disease that is not detectable by two-dimensional echocardiography.

ST Segment “Hump” during Exercise Testing and the Risk of Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy

Background: The appearance of a discrete upward deflection of the ST segment termed “the ST hump sign” (STHS) during exercise testing has been associated with resting hypertension and exaggerated blood pressure response to exercise.

Subclinical skeletal muscle abnormalities in patients with hypertrophic cardiomyopathy and their relation to clinical characteristics.

BACKGROUND Some mutations of cardiac sarcomeric proteins causing hypertrophic cardiomyopathy (beta-myosin heavy chain) are associated with skeletal muscle fiber dysfunction, while subclinical skeletal myopathy can be diagnosed by electromyography (EMG) in a substantial proportion of hypertrophic cardiomyopathy patients. METHODS In 49 consecutive, unrelated patients with hypertrophic cardiomyopathy, conventional EMG of deltoid, vastus lateralis, tibialis anterior and soleus muscles was performed. No patient had clinically detectable muscle weakness. We compared the clinical and echocardiographic characteristics between patients with normal and patients with myopathic EMG. RESULTS Myopathic EMG findings were demonstrated in 13 patients (26.5%), 26 patients (53.1%) had normal findings and 10 patients (20.4%) had indeterminate recordings. There was no significant difference in mean age, maximum wall thickness, left ventricular fraction shortening, NYHA class, the existence of left ventricular outflow tract obstruction, syncope, or the occurrence of nonsustained ventricular tachycardia in the Holter recording among the three groups. Comparison between the myopathic and the normal group revealed that nine patients from the latter (34.6%) had a positive history of sudden death in the family, whereas no patient had such a history in the former group (P=0.015). CONCLUSION The higher prevalence of a family history of sudden death in patients with normal EMG, although not thoroughly explained by our data, may reflect differences in the genetic substrate produced by the higher prevalence of high-risk mutations that are not expressed in skeletal muscle (e.g. troponin T). Further evaluation in genotyped patients is warranted.

Mild left ventricular hypertrophy in essential hypertension: is it really arrhythmogenic?

Left ventricular hypertrophy (LVH) has been associated with an increased incidence of ventricular arrhythmias and sudden cardiac death in hypertensive patients. However, it is not known whether this relationship exists in early asymptomatic hypertensives with mild LVH. We prospectively examined 100 consecutive patients with essential hypertension, 35 without and 65 with mild LVH on echocardiography. All underwent a detailed noninvasive arrhythmia work-up and were subsequently followed-up for 3 +/- 1 years in an ambulatory hypertension clinic. None of the 12-lead electrocardiographic parameters examined differed between the two hypertensive groups. A similarly low incidence of simple forms of ventricular ectopy was present in both groups, whereas complex forms of ventricular ectopy were extremely rare in either group. The signal-averaged electrocardiographic parameters examined were also not significantly affected by the presence of mild LVH. Arrhythmia-related symptoms or malignant ventricular arrhythmia events were not observed in either group of patients during follow-up with antihypertensive treatment. The latter resulted in LVH regression in the 65 patients with mild LVH at baseline. It appears that mild LVH among ambulatory hypertensive patients does not carry an additive arrhythmogenic risk and can be successfully reversed with the appropriate antihypertensive therapy, with no need of additional antiarrhythmic management.

Usefulness of Noninvasive Detection of Left Ventricular Diastolic Abnormalities During Isometric Stress in Hypertrophic Cardiomyopathy and in Athletes

We showed previously that the handgrip apexcardiographic test (HAT) is a useful method for detecting left ventricular (LV) diastolic abnormalities in patients with coronary artery disease and systemic hypertension. This study evaluates the use of HAT for assessing the prevalence and types of exercise-induced diastolic abnormalities in patients with obstructive (n = 31) and nonobstructive (n = 35) hypertrophic cardiomyopathy (HC) as well as its potential value for separating healthy subjects and athletes from patients with HC. We obtained a HAT in 66 consecutive patients with HC and in 72 controls (52 healthy volunteers and 20 athletes). A positive HAT was defined by the presence of one of the following: (1) relative A wave to total height (A/H) during or after handgrip > 21% (compliance type), (2) total apexcardiographic relaxation time (TART) > 143 ms or the heart rate corrected TART (TARTI) during handgrip < 0.14, (relaxation type), (3) both types present (mixed type), and (4) diastolic amplitude time index (DATI = TARTI/[A/D]) during handgrip < 0.27. Of the controls, only 1 of 52 healthy subjects and 1 of 20 athletes showed a positive HAT, whereas of the total HC cohort 63 of 66 patients (95%) had a positive result. There was no significant difference in the distribution of these types between obstructive and nonobstructive HC. Further, no LV diastolic abnormalities were present in 10 of 35 patients (29%) with nonobstructive HC at rest and in 3 of 35 patients (9%) during handgrip, whereas of the patients with obstructive HC only 1 of 31 (3%) had no LV diastolic abnormalities at rest and none during handgrip. Based on HAT data, our study demonstrates that in HC (1) LV diastolic abnormalities are very frequent during handgrip; (2) patients with nonobstructive HC show significantly fewer LV diastolic abnormalities at rest than those with obstructive HC; and (3) no significant difference exists between obstructive and nonobstructive HC in the prevalence of types of handgrip-induced LV diastolic abnormalities. Consequently, HAT appears to be of clinical value as an additional tool for separating normal patients and athletes from patients with HC.

Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy

BACKGROUND Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) in the context of primary prevention remains suboptimal. The purpose of this study was to examine the additional contribution of programmed ventricular stimulation (PVS) on established risk assessment. METHODS Two-hundred-and-three consecutive patients with diagnosed HCM and ≥1 noninvasive risk factors were prospectively enrolled over 19years. Patients were risk stratified, submitted to PVS and received an implantable cardioverter-defibrillator (ICD) according to then-current American Heart Association (AHA) guidelines and inducibility. Participants were prospectively followed-up for primary endpoint occurrence (appropriate ICD therapy or SCD). Contemporary (2015) AHA and European Society of Cardiology (ESC) guidelines were retrospectively assessed. RESULTS During a median follow-up period of 60months the primary endpoint occurred in 20 patients, 19 of whom were inducible and received an ICD. Overall, 79 patients (38.9%) were inducible and 92 patients (45.3%) received an ICD (PVS sensitivity=95%, specificity=67.2%, positive predictive value=24%, negative predictive value=99.2%). AHA and ESC guidelines application misclassified 3 and 9 primary endpoint-meeting patients, respectively. Inducibility was the most important determinant of event-free survival in multivariate Cox regression (hazard ratio=33.3). A combined approach of ESC score≥6% or AHA indication for ICD with PVS inducibility yielded absolute sensitivity and negative predictive value, the former at a more cost-effective and specific way. CONCLUSIONS Inducibility at PVS predicts SCD or appropriate device therapy in HCM. Non-inducibility is associated with prolonged event-free survival, while the procedure was proven safe. Reintegration of PVS into established risk stratification models in HCM may improve patient assessment.