Andrzej Okreglicki

Clinical features, survival experience, and profile of plakophylin-2 gene mutations in participants of the Arrhythmogenic Right Ventricular Cardiomyopathy Registry of South Africa

Little is known about arrhythmogenic right ventricular cardiomyopathy (ARVC) in Africa. The objective of this study was to delineate the clinical characteristics, survival, and genetics of ARVC in South Africa. Information on clinical presentation, electrocardiographic and cardiac imaging findings, histology, and outcome of cases with suspected ARVC was collected using the standardised form of the ARVC Registry of South Africa. Genomic DNA was screened for mutations in plakophylin-2 (PKP2) gene. Survival and its predictors were analyzed using the Kaplan-Meier and Cox proportional hazards regression methods, respectively. Fifty unrelated cases who met the diagnostic criteria for ARVC were enrolled between January 2004 and April 2009. Clinical presentation was similar to that reported in other studies. Annual mortality rate was 2.82%, five-year cumulative mortality rate 10%, and mean age at death 36.9 +/- 14.7 years. Overall survival was similar to the general South African population (P = 0.25). Independent risk factors for death were syncope (Hazard Ratio [HR] 10.73, 95% Confidence Interval [CI] 1.88-61.18, P = 0.008) and sustained ventricular tachycardia (HR = 22.97, 95%CI 2.33-226.18, P = 0.007). Seven PKP2 gene mutations were found in 9/36 (25%) unrelated participants, five being novel. The novel C1162T mutation occurred in four white South Africans sharing a common haplotype, suggesting a founder effect. Compound heterozygotes exhibited a severe phenotype signifying an allele dose effect. ARVC is associated with early mortality that is no different to the general South Africa population whose lifespan is shortened by HIV/AIDS. PKP2 gene mutations are common, have an allele dose effect, and a novel founder effect in white South Africans.

Avoid Delivering Therapies for Nonsustained Fast Ventricular Tachyarrhythmia in Patients with Implantable Cardioverter/Defibrillator: The ADVANCE III Trial

Introduction: The purpose of this investigation is to evaluate whether a prolonged detection interval for life threatening ventricular tachyarrhythmia (VT) is able to reduce therapies (Rx) delivered by an implantable cardioverter/defibrillator (ICD). Until now, only the PREPARE trial demonstrated a reduction of ICD Rx in a cohort of primary prevention patients.

Surgery for ventricular tachycardia of left ventricular origin: risk factors for success and long-term outcome

OBJECTIVESnTo review 26 consecutive patients with sustained monomorphic ventricular tachycardia (VT) of left ventricular origin, who underwent direct VT surgery.nnnMETHODSnEconomic factors precluded the use of an implantable cardioverter defibrillator (ICD) in the majority of these patients, and the indication for surgery in 81% of patients was for failed medical drug therapy and 27% of patients had frequent or incessant life-threatening VT. The principles of direct VT surgery included intraoperative mapping, extended endocardial resection, cryoablation, left ventricular aneurysm repair by left ventricular remodelling and endoaneurysmorrhaphy, as well as coronary artery bypass grafting.nnnRESULTSnTwo patients with non-ischaemic VT were significantly younger (37.7 +/- 19.4 years, P = 0.03), had lower preoperative New York Heart Association class (P = 0.03), and had better left ventricular ejection fractions of 59.5 +/- 2.1% (P = 0.001) than the 24 ischaemic patients. No operative mortality or recurrence of VT occurred in this group. Ischaemic VT patients had an operative mortality of 8.3%; risk factors were concomitant valve surgery (P = 0.02), and perioperative intra-aortic balloon pump (P = 0.02). Surgery improved the left ventricular ejection fraction from 28.4 +/- 9.8% to 43.2 +/- 8.2% (P = 0.0001). Freedom from recurrence or inducibility of VT in operative survivors was 78.8 +/- 9.6% at 10 years; risk factors were arrhythmic focus remote to the left ventricular aneurysm (P = 0.015), and simple cryoablation or endocardial resection alone and not in combination (P = 0.003). Survival was 54.1 +/- 11.6% and 43.3 +/- 13.4% at 5 and 10 years, respectively, and there were no arrhythmic or sudden cardiac deaths. Patients with immediately life-threatening VT unsuitable for ICD implantation requiring urgent or emergent VT surgery had a 10-year survival of 22.2 +/- 13.9% compared to the more elective surgical group with a rate of 73.3 +/- 13.9% (P = 0.08).nnnCONCLUSIONSnDirect VT surgery should remain an objective for symptomatic drug refractory VT of left ventricular origin.

Redefining the ECG in urban South Africans: Electrocardiographic findings in heart disease-free Africans

BACKGROUNDnThe 12-lead electrocardiogram (ECG) represents an important diagnostic tool for detecting heart disease, but the normal ECG in those of African descent has yet to be definitively described.nnnMETHODSnWe systematically analysed 12-lead ECGs from 387 urban South Africans determined to be heart disease free (using the Minnesota code) following advanced cardiologic assessment, including echocardiography, at the Baragwanath Hospital in Soweto, South Africa.nnnRESULTSn123 males (32%, 41.2 ± 14.5 years) and 264 females (37.4 ± 14.2 years) were studied. Most were in sinus rhythm (87%) and had normal axis (89%). Mean interval data were: PR interval (156 ± 28 ms; 95% CI: 153-159 ms), QRS duration (82 ± 16 ms; 95% CI: 80-84 ms), QT interval (379 ± 48 ms; 95% CI: 374-384 ms) and QTc interval (426 ± 32 ms; 95% CI: 423-429 ms). Overall, 199 (51%; 95% CI: 46.0% to 56.0%) subjects had an ECG abnormality or normal variant and 67 ECGs (17%; 95% CI: 13.3% to 20.7%) had major and minor abnormalities. ECG changes normally ascribed to myocardial ischaemia were: i) ST elevation (9.3%; 95% CI: 6.2 to 11.9%), ii) Q waves (7.4%; 95% CI: 4.4 to 9.5%) and iii) ST depression (2.3%; 95% CI: 0.8 to 3.8%). Sokolow-Lyon Index voltage exceeding 38 mm indicative of left ventricular hypertrophy was more prominent in males than females (23.6% vs. 6.4%; OR=4.5; 95% CI: 2.3-8.5).nnnCONCLUSIONSnThese data provide a contemporary reference to the 12-lead ECG in urban South Africans found to be heart disease free, with both major and minor abnormalities detected.

VDD Pacing in Persistent Left Superior Vena Cava

Although persistent left superior vena cava (PLSVC) is the most common major venous anomaly of the heart, associated absence of the right superior vena cava with normal visceral situs is exceedingly rare. Such a patient presented with complete heart block requiring permanent pacing. This was achieved successfully using a single lead VDD system via the PLSVC with atrial sensing in the coronary sinus.

Amiodarone-induced thyroid dysfunction

Background. Little is known about the frequency of thyroid dysfunction (TD) associated with amiodarone therapy in southern Africa. Objectives. To determine the incidence of TD in a cohort of patients initiated on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area. Patients. Pharmacy records were used to obtain the names of patients who received amiodarone between November 1999 and December 2002. Results. The sample size was 194, but data analysis was limited to the 163 patients for whom there were complete data. The mean age ± standard deviation (SD) was 59.0 ± 15.0 years (range 22–89 years). There were 67 female and 96 male patients. The indications for amiodarone therapy were supraventricular tachycardias (N = 102, 62.6%), ventricular tachycardia (N = 55, 33.7%), and prophylaxis against tachycardias (N = 3, 1.8%). The indication was uncertain in 3 patients (1.8%). The median duration of amiodarone treatment was 679.0 days (quartile deviation (QD) 1 172 days, range 3–6 425 days) in the whole cohort. The median duration of amiodarone therapy until new TD was 943 days (QD 1 185 days), significantly longer than in patients who remained euthyroid (547 days, QD 1 135 days) (P = 0.05). There were 45 new TD cases (27.6%): 11 patients (6.7%) were thyrotoxic, 1(0.6%) transient thyrotoxicosis, 1 (0.6%) subclinical hyperthyroidism, 13 (8.0%) had subclinical hypothyroidism, 12 (7.4%) hypothyroidism and 7 (4.3%) had minor changes in thyroid function. Conclusions. We found a high incidence of new-onset TD, similar to the highest rates reported internationally. Local factors responsible for this need to be investigated.

The clinical, electrocardiographic and echocardiographic characteristics and long-term outcome of patients with tachycardia-induced cardiomyopathy.

Introduction The clinical, electrocardiographic and echocardiographic features and long-term outcome of patients with tachycardia-induced cardiomyopathy (TIC) have not been well described in the past. Methods A retrospective study was performed at our institution of patients with a diagnosis of TIC. Results Thirty-three patients with pure TIC and 12 patients with impure TIC were identified. Compared to patients with dilated cardiomyopathy (DCMO), pure TIC patients were less symptomatic, as judged by NYHA class (p = 0.02), they had fewer clinical signs of heart failure (p = 0.007) and were more likely to report palpitations (p = 0.007) at presentation. Electrocardiographically, pure TIC patients had fewer Q waves (p = 0.002), less left ventricular hypertrophy (LVH) (p = 0.004) and repolarisation abnormalities (p = 0.048), and shorter QRS durations (p = 0.024). Echocardiographically, pure TIC patients had significantly smaller left ventricular internal diameter in diastole (LVIDd) (p < 0.001), ventricular internal diameter in systole (LVIDs) (p = 0.001) and left atrial dimensions (p = 0.048) at presentation compared to DCMO patients. Patients with pure TIC had a trend towards increased residual LVIDd dimensions compared to a control group with normal echocardiograms, indicating a persistence of adverse LV remodelling late after control of the causative tachycardia (p = 0.06). Recurrent tachycardia occurred in three patients, which resulted in a precipitous decline in left ventricular ejection fraction (LVEF). Conclusions This study is the first to compare features of pure and impure TIC. Patients with pure TIC had shorter QRS durations, fewer Q waves, and less LVH and repolarisation abnormalities at presentation compared to DCMO patients. TIC patients tended to have smaller LVIDd dimensions at presentation and have persistence of adverse LV remodelling, as characterised by persistent enlargement of LVIDd dimensions, at late follow up.

Sport and Arrhythmogenic Right Ventricular Cardiomyopathy

Sudden deaths have been reported in sportspersons and have been related to physical activity. It is possible that exercise may be a trigger of potentially lethal arrhythmias in susceptible individuals or may be the factor that converts a defect of genotype to an abnormal and arrhythmogenic phenotype. Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)may be at higher risk of sports-related arrhythmias and sudden death. In the South African ARVC registry,56% of patients were involved in regular sport participation. Various potential mechanisms linking sport and exercise to arrhythmias in patients with ARVC may exist.

PACE – Prevent Arrhythmic Cardiac Events

Sudden Cardiac Deaths or Arrests (SCD or SCA) are not just random events or a cruel “luck of the draw”. In fact, they may be predictable, and in that case usually preventable; and the event itself may be reversible.(1) This, therefore, deserves our attention and awareness. Armed with this knowledge, intervention may not only protect those who have experienced and survived an SCD or SCA event from a repeat episode but may also identify those, often apparently well, who are at risk from dying suddenly.

Arrhythmias and electrophysiology: The State of the Nation

For far too long in South Africa, cardiac electrophysiology and an interest in arrhythmias has been treated like an orphaned infant of a distant relative, only to be tolerated in the home of cardiology where cardiac intervention, understood mainly as “plumbing”, is considered to be the favored son and heir. Yet, elsewhere, the fi eld of arrhythmias and cardiac electrophysiology (EP) has grown exponentially, arrhythmia and heart rhythm societies have passed their coming of age and EP is a recognized and certifi able subspecialty of cardiology. It is time, therefore, that EP, the “cardiac-electrician” son, be accepted and be accorded due respect, nurturing and equal opportunity in the South African family of cardiology.