Electrocardiographic Characteristics and Their Correlation with Echocardiographic Alterations in Fabry Disease.

Fabry disease (FD) is an X-linked disorder with α-galactosidase A deficiency. Males (>30 years) and females (>40 years) often present with cardiac manifestations, predominantly left ventricular hypertrophy (LVH). The aim of this study was to evaluate electrocardiographic (ECG) characteristics within FD patients to identify gender related differences, and to additionally explore the association of ECG parameters with structural and functional alterations on transthoracic echocardiography (TTE). Retrospective cross-sectional analysis of 45 FD patients with contemporaneous ECG and TTE was performed and compared to age and gender matched healthy controls. FD patients demonstrated alterations in several ECG parameters particularly in males, including prolonged P-wave duration (91 vs. 81 ms, p = 0.022), prolonged QRS duration (96 vs. 84 ms, p < 0.001), increased R-wave amplitude in lead I (8.1 vs. 5.7 mV, p = 0.047), increased Sokolow-Lyon index (25 vs. 19 mV, p = 0.002) and were more likely to meet LVH criteria (31% vs. 7%, p = 0.006). FD patients with impaired basal longitudinal strain (LS) on TTE were more likely to meet LVH criteria (41% vs. 0%, p = 0.018). Those with more advanced FD (increased LV wall thickness on TTE) were more likely to meet LVH criteria but additionally demonstrated prolonged ventricular depolarization (QRS duration 101 vs. 88 ms, p = 0.044). Therefore, alterations on ECG demonstrating delayed atrial activation, delayed ventricular depolarization and evidence of LVH were more often seen in male FD patients. Impaired basal LS, a TTE marker of early cardiac involvement, correlated with ECG abnormalities. Increased LV wall thickness on TTE, a marker of more advanced FD, was associated with more severe ECG abnormalities.

Basal Segmental Longitudinal Strain: A Marker of Subclinical Myocardial Involvement in Anderson-Fabry Disease.

BACKGROUND: Cardiac involvement in Anderson-Fabry disease (AFD) is associated with increased left ventricular (LV) wall thickness. The aim of this study was to evaluate if two-dimensional global and regional strain in patients with AFD can identify early myocardial involvement (when LV wall thickness and function are normal). Additionally, the association of altered strain with adverse cardiovascular events was evaluated. METHODS: In a retrospective cross-sectional study, 43 patients with AFD, before enzyme replacement therapy (mean age, 44 ± 12 years; 58.1% men), were compared with age- and gender-matched healthy control subjects. The mean follow-up duration among patients with AFD for major adverse cardiovascular events (MACE) was 82 months. RESULTS: LV ejection fraction was similar between groups (patients with AFD vs control subjects, 61 ± 8% vs 61 ± 6%; P = .89). However, global longitudinal strain (LS) was impaired in patients with AFD compared with control subjects (-16.5 ± 3.8% vs -20.2 ± 1.7%, P < .001), with greater impairment in patients with AFD with increased LV wall thickness (-15.4 ± 3.9% vs -18.7 ± 2.3%, P < .006). Additionally, LS was most impaired in the basal segments in patients with AFD (-14.8 ± 3.7% vs -20.3 ± 1.1%, P < .001). MACE occurred in 19 of 43 patients (four women, 15 men), and Kaplan-Meier analysis demonstrated that MACE were associated with impaired basal LS. CONCLUSIONS: In patients with AFD, altered basal LS is present even in those with normal LV wall thickness and is associated with MACE. Therefore, basal LS should be considered when screening for cardiac involvement in AFD, particularly in female patients with AFD with normal LV wall thickness.

Klinefelter syndrome with fabry disease--a case of nondisjunction of the X-chromosome with sex-linked recessive mutation.

A 52 year-old male with Klinefelter syndrome presented with chest tightness and rapid atrial fibrillation with hypotension. His echocardiogram demonstrated symmetrical left ventricular hypertrophy with minimal diastolic dysfunction. Subsequent investigations confirmed the diagnosis of Fabry cardiomyopathy. This is the first reported case of Klinefelter syndrome with homozygous sex-linked recessive mutation presenting primarily with cardiac manifestation.

Left atrial enlargement and reduced atrial compliance occurs early in Fabry cardiomyopathy.

BACKGROUND: Fabry disease is associated with left ventricular hypertrophy (LVH) and myocardial fibrosis. The aim of this study was to evaluate left atrial (LA) size and function using tissue Doppler-derived strain in patients with Fabry disease. METHODS: Echocardiography was performed in 33 Fabry patients (14 without LVH, 19 with LVH) before commencement of enzyme replacement therapy, and results were compared with those from age-matched and gender-matched controls (n=28 and n=38, respectively). Atrial strain and strain rate were measured from four segments in the apical four-chamber and two-chamber views of the LA, and global values were calculated. Systolic strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate were measured. Phasic LA volumes and fractions were calculated. Mitral inflow and tissue Doppler E' velocities were used to estimate left ventricular (LV) diastolic function. RESULTS: LA volume was increased in Fabry patients, even in the absence of LVH. Importantly, diastolic function was normal in this subgroup without LVH, with E' velocities similar to those in controls. LA systolic strain and early diastolic strain rate were selectively reduced in Fabry patients with LVH and reflect reductions in LA and LV relaxation, respectively, consequent to increased LV mass. However, independent of LVH, both Fabry groups had significant reductions in systolic strain rate and increased LA stiffness index. CONCLUSIONS: Fabry disease is associated with LA enlargement and reduced atrial compliance that occurs before the development of LVH. This suggests that Fabry cardiomyopathy may not only cause ventricular hypertrophy and fibrosis but also alters atrial myocardial properties early in the disease process. Consequently, measurements of LA size and function may be useful in the early diagnosis of Fabry disease, before the development of LVH.

A rare association of pulmonary hypertension and dextrocardia with Poland syndrome.

Poland syndrome is a rare congenital abnormality with an estimated incidence of 1 in 20,000 to 1 in 30,000 live births. We report and discuss this rare combination of pulmonary hypertension and dextrocardia with Poland syndrome. This case report also highlights the underlying pathogenetic mechanisms during foetal development and the potential to misdiagnose cardiac ischaemia in a patient with an anatomic anomaly.

Effect of reperfusion time on inducible ventricular tachycardia early and spontaneous ventricular arrhythmias late after ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Prompt thrombolytic reperfusion reduces postinfarct ventricular electrical instability after ST elevation myocardial infarction (STEMI). OBJECTIVE: The purpose of this study was to examine the relationship between reperfusion time and inducible ventricular tachycardia (VT) early and spontaneous ventricular arrhythmias (VAs) late after primary percutaneous coronary intervention (PCI) for STEMI. METHODS: Consecutive patients were recruited if they (1) had no prior coronary disease, (2) had been reperfused with primary PCI, (3) had postinfarct ejection fraction ≤40%, and (4) had undergone cardiac electrophysiologic study (n = 128). Three groups were compared according to reperfusion time: early (≤3 hours, n = 26), intermediate (>3-5 hours, n = 45), or delayed reperfusion (>5 hours, n = 57). Spontaneous VA was a composite endpoint of sudden death or defibrillator-treated VA. RESULTS: Mean ejection fraction (33% ± 5%, 31% ± 6%, and 31% ± 7%, P = .41) and peak creatinine kinase (P = .37) were similar between groups. VT was inducible in 11.5%, 17.8%, and 36.8% of patients in the early, intermediate, and delayed reperfusion groups, respectively (P = .003). At 2 years, the incidence of spontaneous VA was 0%, 8.9%, and 14% in the early, intermediate, and delayed reperfusion groups, respectively (P = .025). By multivariable analysis, delayed reperfusion conferred a sixfold increase in the odds of inducible VT (P = .01). Although inducible VT was the strongest predictor of spontaneous VA (hazard ratio 14.31, P = .001), delayed reperfusion conferred a threefold increase in risk when inducible VT was excluded from the multivariable model (P = .035). CONCLUSION: Reperfusion time is a critical determinant of postinfarct ventricular electrical instability early and late after STEMI treated with primary PCI.

Predictive value of ST resolution analysis performed immediately versus at ninety minutes after primary percutaneous coronary intervention.

ST segment resolution (STR) predicts epicardial and microvascular reperfusion after primary percutaneous coronary intervention (PPCI) or thrombolysis for ST-elevation myocardial infarction. Immediate restoration of epicardial coronary flow, with improved microvascular perfusion, is much more likely with PPCI. However, the predictive value of immediate STR compared to 90 minutes after PPCI remains unknown. In 622 consecutive patients with ST-elevation myocardial infarction (mean age 59 +/- 13 years), 217 had complete STR immediately after PPCI (group A), 188 had complete STR only at 90 minutes (group B), and 217 had incomplete STR at either point (group C). The primary end point was mortality and adverse cardiovascular events ([MACE] death, nonfatal repeat myocardial infarction, and heart failure). Group A had a greater left ventricular ejection fraction (53%, 47%, and 46%, p <0.001) and lower all-cause mortality (1.8%, 3.2%, and 6%, p = 0.07), lower heart failure (1.8%, 4.3%, and 7.8%, p <0.001), and MACE (5.1%, 9.6%, and 16.1%, p = 0.001) at 30 days compared to groups B and C, respectively. The rate of MACE at 1 year was 7.6%, 17.1%, and 20.2% in groups A, B, and C, respectively (p <0.001). Immediate STR independently predicted MACE (adjusted hazard ratio 0.36, 95% confidence interval 0.21 to 0.61, p = 0.001, group A vs C), and STR at 90 minutes did not. In conclusion, STR analysis performed immediately after PPCI provided superior differentiation for adverse cardiovascular events compared to STR at 90 minutes. Immediate STR should be the contemporary goal of reperfusion with PPCI.

Prognostic impact of Q waves on presentation and ST resolution in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

Q waves can develop early in infarction and indicate infarct progression better than symptom duration. ST resolution (STR) is a predictor of reperfusion success. Our aim was to assess the prognostic impact of Q waves on presentation and STR after primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. The combined end point was of mortality and adverse cardiovascular events (MACE; death, repeat myocardial infarction, or heart failure). Q waves on presentation (Q wave, n = 332; no Q wave, n = 337) was associated with significantly less mean STR, greater incidence of akinetic, dyskinetic, or aneurysmal regional wall motion, lower left ventricular ejection fraction, and worse in-hospital and 1-year MACEs (1 year 24% vs 8.2%, p <0.001). In addition, Q waves on presentation compared to no Q waves were associated with worse 1-year MACE regardless of infarct presentation in < or =3 hours, infarct location, and adequate STR (> or =70%). Q waves on presentation and inadequate STR (<70%), but not symptom duration, were independent predictors of MACE by multivariable analysis (adjusted hazard ratios of 2.7 and 2.4 for Q waves and STR, respectively). Compared to group A (no Q waves on presentation with STR), patients in group B (no Q waves with inadequate STR), group C (Q waves with STR), and group D (Q waves with inadequate STR) had hazard ratios of 3.0, 3.6, and 7.7, respectively (p <0.05) for the occurrence of MACE. In conclusion, assessment of Q-wave status on presentation and STR immediately after PPCI provides a simple and early clinical predictor of outcomes in ST-elevation myocardial infarction.

Effect of prehospital triage on revascularization times, left ventricular function, and survival in patients with ST-elevation myocardial infarction.

Shorter reperfusion times lead to better outcomes in patients with ST-elevation myocardial infarction (STEMI). We assessed the efficacy of prehospital triage with bypass of community hospitals and early activation of the cardiac catheterization team on revascularization times, left ventricular (LV) ejection fraction, and survival. Patients with STEMI (624) were divided into 3 groups determined by site of triage: ambulance field triage (163), interventional center emergency department (202), and 3 community hospital emergency departments (259). Compared with community hospital and interventional center triages, ambulance field triage resulted in a significant median decrease in door-to-balloon times of 68 and 27 minutes, respectively (p <0.001). LV ejection fraction was highest in the field triage group (52 +/- 13%) compared with the interventional center (49 +/- 12%) and community hospital (48 +/- 12%, p = 0.017) groups. Thirty-day mortality was lowest in the ambulance field group (3%) compared with the interventional facility (11%) and community hospital (4%, p = 0.007) groups. There was a significant difference in long-term survival with up to 30-month follow-up among the 3 triage groups (p = 0.041). With time-dependent Cox regression modeling the difference in survival was significant only during the first week after STEMI (p = 0.020). Every extra minute of symptom onset to reperfusion time was associated with a relative risk of long-term mortality of 1.003 (95% confidence interval 1.000 to 1.006, p = 0.027). In conclusion, field triage of patient with STEMI decreased revascularization times, which preserved LV function, and improved early survival.

Clinical and electrocardiographic correlates of normal coronary angiography in patients referred for primary percutaneous coronary intervention.

This study sought to determine the prevalence as well as clinical and electrocardiographic correlates of patients referred for primary percutaneous coronary intervention (PCI) who had angiographically normal coronary arteries. Data for 690 consecutive patients with ST-elevation myocardial infarction (STEMI) referred for primary PCI within a metropolitan area health service were reviewed. Characteristics of patients with angiographically normal coronary arteries (n = 87; 13%) were compared with patients with angiographically shown culprit lesions (control group; n = 594). Nine patients with significant coronary disease, but no identifiable culprit lesion, were excluded. Electrocardiograms (ECGs) from both groups were reviewed by 2 cardiologists blinded to angiographic findings. Patients in the normal coronaries group were younger and had fewer risk factors. On expert review of ECGs, 55% of patients in the normal coronaries group had ST-elevation criteria for STEMI (vs 93% in the control group; p <0.001), but the ECG was considered consistent with a diagnosis of STEMI by both observers in only 33% (vs 92% in the control group; p <0.001). Left branch bundle block independently correlated with normal coronary arteries on multivariate analysis (odds ratio for STEMI 0.016, 95% confidence interval 0.004 to 0.064, p <0.001). The discharge diagnosis in the normal coronaries group was predominantly pericarditis (n = 72; 83%). In conclusion, the prevalence of angiographically normal coronary arteries in patients referred for primary PCI was 13%. Electrocardiographic correlation suggested that this can be reduced by adherence to conventional electrocardiographic criteria for STEMI diagnosis and review of ECGs by experienced clinicians.

Cardiovascular manifestations in Fabry disease: a clinical and echocardiographic study.

This study reviews the clinical and echocardiographic findings in a cohort of Fabry patients (n=12) and compares echocardiographic findings to normal controls. Almost all patients had extracardiac manifestations. Five out of 12 patients had cardiovascular symptoms. Nine out of 12 patients had left ventricular hypertrophy (LVH) on the electrocardiogram (ECG) and one patient had short PR interval. Three patients had epicardial coronary disease. Four patients had 'rat-tail' appearance on left ventriculogram. Six patients who had myocardial biopsy showed extensive vacuolation of the myocytes on light microscopy and concentric, myelinoid lamellar cytoplasmic inclusion bodies on electron microscopy. On echocardiography, LV mass was significantly increased in the Fabry group compared to normal controls. Traditional parameters of diastolic function including peak E velocity, peak A velocity and deceleration time were no different to normal controls. The IVRT was significantly prolonged in the Fabry subjects. The PV atrial reversal duration exceeded that of mitral A wave duration in the Fabry group. The septal E' velocity with Doppler tissue imaging (DTI) was significantly lower in the Fabry group than the normal controls. Fabry disease should be considered in the differential diagnosis in patients with unexplained LVH and late onset hypertrophic cardiomyopathy. Extracardiac manifestations are common.