Temporal patterns of progression and regression of electrical and mechanical remodeling of the atrium.

OBJECTIVES: We evaluated serial changes of electrical and mechanical parameters of atrial remodeling in dogs subjected to rapid atrial pacing. BACKGROUND: Prolonged rapid atrial excitation causes electrical and mechanical remodeling, which contributes to persistence of atrial fibrillation and clot formation. However, the temporal relationship between these two types of atrial remodeling remains unknown. METHODS: In 8 dogs, rapid pacing at 400 ppm was continued for 14 days. The electrophysiologic and transesophageal echocardiographic studies were performed on the day before and after 2, 7, and 14 days of rapid pacing, then 1 and 7 days after the cessation of pacing. These were compared with sham-operated dogs (instrumented but not paced, n=6). RESULTS: With rapid pacing, there was an immediate shortening of the effective refractory period (ERP) and decreases in the transmitral atrial wave velocity (MAV) and the left atrial appendage emptying velocity (LAAV). In contrast, conduction velocity (CV) decreased and the left atrial appendage area (LAAA) increased progressively over 14 days. During the recovery, ERP, MAV, and LAAV returned to the baseline in 1 day, whereas CV and LAAA did in 7 days. ERP was highly positively correlated with LAAV (r=0.78, p<0.001) and MAV (r=0.73, p<0.001), while CV was negatively correlated only with LAAA (r=-0.58, p<0.001). CONCLUSIONS: Pacing-induced electrical and mechanical remodeling of the atrium exhibits divergent patterns of progression and regression such that changes of ERP and contractile function take place more rapidly than those of CV and atrial size.

Primary stenting for left-main shock syndrome.

AIMS: Acute myocardial infarction (AMI) complicated by unprotected left-main shock (LMS) remains a highly morbid event among acute coronary syndromes. Whether early percutaneous coronary intervention (PCI) in the stent era improves the clinical outcome remains poorly defined. METHOD AND RESULTS: 25 consecutive patients who presented with LMS were treated by primary stenting of bare metal stents for the unprotected left main lesion with an aid of conventional supportive measures. Mean age of the patients was 67 (range, 46-89), 84% were male, with an initial mean systolic BP of 88mmHg (range, 40-120), HR of 82 bpm (range, 38-130), and symptom onset to reperfusion of 4.8hours (range, 1.5-17). An initial TIMI grade 0 flow was noted on the emergent CAG among 56% of the patients, but after PTCA and stenting, TIMI grade 3 flow was obtained among 84%. 30-day mortality was 32%, while one patient underwent emergent CABG for subacute stent thrombosis and 3 patients required elective CABG for residual disease during admission. Among 11 patients who were discharged alive, one required further institutionalization for ischemic brain injury, and the 2 required target vessel revascularization for restenoses. The major adverse cardiac events (death, re-infarction, stroke, and target vessel revascularization) occurred in 68% (17/25) over a 12-month follow-up, including 40% of mortality. CONCLUSIONS: AMI complicated by unprotected LMS could be treated effectively with a prompt application of stenting and result in an acceptable mortality and morbidity.

A comparison between calcium channel blocking drugs with different potencies for T- and L-type channels in preventing atrial electrical remodeling.

Calcium overload plays a key role in the development of atrial electrical remodeling. The effect of an L-type Ca channel blocker in preventing this remodeling has been reported to be short lasting, partly due to down-regulation of this channel and persisting Ca entry through the T-type Ca channel. To prove if efonidipine, a dual L- and T-type Ca channel blocker exerts a greater effect than an L-type Ca channel blocker verapamil, 21 dogs underwent rapid atrial pacing at 400 bpm for 14 days, pretreatment with efonidipine in 7 (E), verapamil in 7 (V), and none in 7 (C). We measured the atrial effective refractory period (ERP) serially during 14 days of rapid pacing. In response to rapid pacing, ERP decreased progressively in C. In contrast, in E and V, ERP remained greater than ERP in C (P < 0.01) on days 2 through 7. However, on the 14th day, ERP in V decreased to the level seen in C, whereas ERP in E remained significantly longer than ERPs in C or V (P < 0.01). The blockade L-type Ca channel alone is not sufficient, but the addition of a T-type Ca channel blockade shows a more sustained effect to prevent atrial electrical remodeling.

Oral verapamil attenuates the progression of pacing-induced electrical and mechanical remodeling of the atrium.

BACKGROUND: Calcium overload plays a major role in the development of electrical and mechanical remodeling during atrial fibrillation, but the potential of verapamil, a Ca blocker, for preventing atrial electrical remodeling remains controversial. METHODS AND RESULTS: Pacing and recording electrodes were sutured to the right atrium in 16 dogs. After a 5-day recovery period, rapid atrial pacing at 400 ppm was initiated in 8 dogs (control group). In the remaining 8 dogs, oral administration of verapamil (8 mg/kg per day) was started 1 week before the initiation of rapid pacing (verapamil group). On the day before and at 2, 7, 14 days after rapid pacing, electrophysiological (EP) and transesophageal echocardiographic (TEE) studies were performed under autonomic blockade. In response to rapid pacing, EP and TEE parameters changed progressively in the control group (p<0.05 vs day 0), whereas in the verapamil group, no significant changes in the various parameters were observed for the first 7 days. However, verapamil failed to prevent progression of both types of remodeling after 14 days of pacing. CONCLUSION: Verapamil can attenuate the progression of electrical and mechanical remodeling of the atrium for at least 7 days.

Daily oral verapamil before but not after rapid atrial excitation prevents electrical remodeling.

BACKGROUND: Intravenous verapamil has been reported to prevent electrical remodeling induced by rapid atrial excitation of several minutes to several hours. However, the clinical efficacy of verapamil when taken orally and daily remains controversial. PURPOSE: We attempted to demonstrate our hypothesis that if verapamil prevents calcium (Ca) overload, its efficacy would be greater when taken before, rather than after, the onset of rapid atrial excitation. METHODS: In 24 dogs, pacing and recording electrodes were sutured onto the right atrium. After a 5-day recovery period, rapid atrial pacing at 400 ppm was started, followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After group; A). In another eight dogs, oral verapamil administration was begun 1 week before the initiation of rapid pacing (Before group; B). In the remaining eight dogs, only rapid atrial pacing was started, without oral verapamil (Control group; C). We measured the effective refractory period (ERP) and conduction velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing. RESULTS: In response to rapid atrial pacing, ERP, CV, WL decreased and progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these parameters did not change significantly and remained greater than those in A and C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05). The inducibility of AF tended to be lower, and the fibrillation cycle length was longer in B than in A and C. CONCLUSIONS: Oral verapamil started before but not after rapid atrial excitation prevents electrical remodeling. Verapamil may exert beneficial effects when it is taken during sinus rhythm, but not after more than 2 days of atrial tachyarrhythmia.