Angina in fabry disease reflects coronary small vessel disease.

BACKGROUND: Chest pain is frequently reported in Fabry disease (FD). However, its mechanism and clinical relevance are unclear. METHODS AND RESULTS: Basal troponin I level, exercise stress test, single-photon emission computed tomography imaging with (99m)Tc sestamibi, coronary angiography with thrombolysis in myocardial infarction (TIMI) frame count and left ventricular angiography and endomyocardial biopsy were obtained in 13 patients with FD with angina. Ratio of external to lumen diameter of intramural arteries (E/L ratio), myocyte diameter, and extent of fibrosis were morphometrically evaluated by using tissue sections. Controls for coronary angiography and histology were 25 patients with FD without angina and 20 mitral stenosis patients with normal left ventricular function. Troponin I level was elevated in 6 of the 13 patients. Exercise stress test showed evidence of myocardial ischemia, and single-photon emission computed tomography was positive for stress-induced perfusion defects in all patients with FD with angina. Epicardial coronaries were structurally normal but showed slow flow in all and were associated with aneurisms of posterior left ventricular wall in 3 cases. Histology showed remarkable lumen narrowing of most intramural arteries (mean E/L ratio=3.5+/-1.2; P<0.001 versus both control groups), because of hypertrophy and proliferation of smooth muscle and endothelial cells, both engulfed by glycosphingolipids. Replacement fibrosis exceeded that of both controls (P<0.001). Small vessel disease correlated with coronary slow flow and extent of fibrosis, but did not with patients' age, sex, and degree of left ventricular hypertrophy. CONCLUSIONS: patients with FD with angina have perfusion defects, slow coronary flow, and luminal narrowing of intramural arteries. Small vessel disease may contribute to symptomatic limitation and progressive myocardial dysfunction.

Coronary artery bypass grafting for Fabry's disease: veins more suitable than arteries?

Coronary artery bypass grafting was performed in a 54-year-old man affected by untreated Fabry's disease. Left internal mammary artery (LIMA) and saphenous vein grafts were implanted. Surgical samples of LIMA revealed diffuse glycosphyngolipid infiltration of smooth muscle cells, whereas SV was normal. After surgery, the patient received antithrombotic and enzyme replacement therapy. At 1-year follow-up, LIMA graft occluded, whereas saphenous vein graft remained patent. In Fabry's disease, veins, probably because of a low pressure load, seem to be spared from glycosphingolipid accumulation and are more suitable than arteries for grafting. A preventive histology of conduits is suggested before graft selection.

Atrial tachyarrhythmia burden modelling by some electrophysiological parameters in pacemaker-recipient patients with Brady-Tachy syndrome.

AIMS: (1) To correlate atrial tachyarrhythmia (AT) burden of pacemaker-recipient Brady-Tachy syndrome (BTS) patients with a number of diagnostics-derived parameters after 1 month of DDD pacing; (2) to asses whether the activation of atrial overdrive or conventional rate-responsive pacing may affect relevant variables and their correlation. METHODS AND RESULTS: After 1 month of DDD pacing, rate-responsive function or persistent atrial overdrive was randomly activated for 3 months, in 92 BTS patients. Some pacemaker diagnostics parameters collected at 1- and 4-month follow-ups were included in multiple linear regression models, whose dependent variable was the Log transformation of AT burden and compared. With 1-month data, the only variables significantly correlating with Log AT burden were average (with a regression coefficient estimate of -0.07, P=0.02) and standard deviation (0.10, P=0.007) of atrial rate, mean premature atrial contraction (PAC) coupling interval (CI) (-0.005, P=0.001), frequency of PACs with CI<500 ms (1.30, P<10(-6)). Atrial pacing percentage (APP) and ventricular pacing percentage (VPP), PACs with CI>500 ms did not significantly correlate. Four-month data largely confirmed these results, except that in DDDR atrial rate average and standard deviation no longer correlated. Overdrive significantly increased APP and reduced PACs with CI>500 ms. CONCLUSION: AT burden showed significant dependence in DDD and during overdrive on atrial rate average and standard deviation. Highly premature PACs always significantly correlated with AT burden. Though increasing APP, which unexpectedly never correlated, overdrive could only reduce less premature PACs.

Slow coronary flow and stress myocardial perfusion imaging. Different patterns in acute patients.

OBJECTIVE: We investigated myocardial perfusion in acute patients with slow coronary flow (SCF) at angiography. Whether impaired myocardial perfusion occurs in acute patients with SCF is unknown. METHODS: We enrolled 28 consecutive patients with SCF in the epicardial coronary arteries with no evidence of significant stenosis. SCF affected a single coronary artery in 14 patients (group A) and all three coronary vessels in 14 others (group B). Coronary angiography was repeated after dipyridamole infusion and single photon emission computed tomography was performed using dipyridamole as the stress agent. The Thrombolysis in Myocardial Infarction frame count was measured in SCF vessels at baseline and after dipyridamole infusion. RESULTS: Mean Thrombolysis in Myocardial Infarction frame count significantly decreased after dipyridamole in both groups. At baseline, mean values of the single photon emission computed tomography score were 31.5 +/- 1.6 and 25.1 +/- 2.1 in groups A and B, respectively. After dipyridamole, they increased from 31.5 +/- 1.6 to 37.8 +/- 1.4 (P < 0.001) in group A, whereas a further decrease to 15.0 +/- 1.2 (P < 0.005) was observed in group B. CONCLUSIONS: An opposite behavior of myocardial perfusion was observed after dipyridamole infusion: a normal response in patients with SCF affecting one single coronary artery versus an ischemic-like response in those with CSF affecting all three coronary arteries.

Effect of pacemaker rate-adaptation on 24 h beat-to-beat heart rate and blood pressure profiles.

AIMS: The aims of the study were to evaluate the 24-h beat-to-beat heart rate (RR) and blood pressure changes during closed loop stimulation (DDD-CLS) pacing and conventional fixed rate DDD pacing with respect to spontaneous activity. METHODS: We simultaneously and continuously measured beat-to-beat heart rate and blood pressure for 24 h in patients implanted with Inos2+ (Biotronik GmbH, Berlin, Germany). A randomised cross-over comparison of DDD-CLS and DDD pacing was performed by short- and long-term analyses. RESULTS: Seventeen patients (10 males, aged 46-85 years) were enroled in the study: 11 completed the protocol. The percentage of atrial stimulation was 72.87% during DDD-CLS and 38.36% in DDD (P=0.003). All patients were 100% stimulated in the ventricle. On average, the percentage increase of paced RR intervals with respect to spontaneous beats was only 7.4% in DDD-CLS but 20.1% in DDD (P=0.0001). A significant correlation between spontaneous and paced RR profiles was obtained only during DDD-CLS (r(DDD-CLS)=0.77, r(DDD)=0.23, P=0.01). Short-term analysis revealed a 3.79% reduction of the escape interval in DDD-CLS and 8.19% in DDD, and the relative fall in diastolic blood pressure was 1.14% in DDD-CLS and 3.81% in DDD. CONCLUSION: DDD-CLS provided physiological heart rate fluctuations throughout the 24-h test. The blood pressure profiles of paced and spontaneous beats were comparable. The onset of paced rhythm in DDD-CLS resulted in a less pronounced decrease in heart rate and fall in diastolic pressure than in DDD.

Enoximone very low-dose dobutamine stress echocardiography: a new test for detecting viability in severe myocardial dysfunction after acute myocardial infarction.

Relying on the synergistic action on contractility of enoximone and dobutamine when concomitantly infused, 25 patients with their first acute Q-wave anterior myocardial infarctions underwent conventional low-dose dobutamine echocardiography (LDE) and enoximone very-LDE to assess myocardial viability in severely dysfunctioning areas. Images were recorded at peak of pharmacodynamic effect of drugs and 4 months after revascularization. At peak-dose stage of LDE and enoximone very-LDE the regional infarct zone wall-motion score significantly decreased from the basal value of 25.6 +/- 2.9 to 16 +/- 6.0 (P <.001) and to 14.5 +/- 5.2 (P <.001), respectively. A high correlation was found by comparing the wall-motion score of each patient calculated at peak effect of combined drug administration with follow-up values (r(s) = 0.9). Enoximone very-LDE has proven to be a new test useful to evaluate viability in asynergic segments especially when the results of conventional tests are questionable.

Programmed electrical stimulation and Amiodarone therapy for the control of persistent junctional tachycardia.

The use of radiofrequency as a means of synchronization and stimulation does not necessitate an external lead, and thus has allowed the construction of an implantable device for long-term treatment of reentry tachycardias. The device is used along with Amiodarone therapy and can be triggered by the patient himself.