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Background— Sarcoplasmic reticulum (SR) Ca 2+ leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy to HF are still controversial. Methods and Results— We investigated healthy control myocardium (n=5) and myocardium from patients with compensated hypertrophy (n=25) and HF (n=32). In hypertrophy, Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both phosphorylated RyR2 at levels that were not different from healthy myocardium. Accordingly, inhibitors of these kinases reduced the SR Ca 2+ leak. In HF, however, the SR Ca 2+ leak was nearly doubled compared with hypertrophy, which led to reduced systolic Ca 2+ transients, a depletion of SR Ca 2+ storage and elevated diastolic Ca 2+ levels. This was accompanied by a significantly increased CaMKII-dependent phosphorylation of RyR2. In contrast, PKA-dependent RyR2 phosphorylation was not increased in HF and was independent of previous β-blocker treatment. In HF, CaMKII inhibition but not inhibition of PKA yielded a reduction of the SR Ca 2+ leak. Moreover, PKA inhibition further reduced SR Ca 2+ load and systolic Ca 2+ transients. Conclusions— In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca 2+ leak. In the transition from hypertrophy to HF, the diastolic Ca 2+ leak increases and disturbed Ca 2+ cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction.

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Background: Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE), it is still used as an adjunct to coronary artery bypass grafting (CABG). This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed.

From 1970 to 1990, 71 consecutive patients (51 men and 20 women) had pericardectomy for chronic constrictive pericarditis. The mean age was 44.2 +/- 16.1 years. In the preoperative state 2.8% were in NYHA class I, 18.3% in II, 43.6% in III and 35.2% in IV. The operative approach was median sternotomy in 93% and left anterolateral thoracotomy in 7%. The early mortality rate (within 30 days after operation) was 5.6%. All four early deaths were female (P < 0.001), in the preoperative state the patients were classified as NYHA class IV (P < 0.01). These patients had a significantly higher preoperative mean right atrial pressure then survivors (21.5 +/- 8.5 mmHg vs 13.6 +/- 5.6 mmHg, P < 0.005). Follow-up was obtained for 65 patients (91.5%) and averaged 11 +/- 5.8 years (the longest period was 21.5 years). Actuarial survival at 5, 10, 15 and 20 years for all patients was 84.6% +/- 4.5%, 80.1% +/- 5.3%, 70.5% +/- 6.9% and 65.8% +/- 7.9%, respectively. In the preoperative state 10 of the 12 late deaths (83%) were classified NYHA class IV and the remaining ones class III. Of the 49 patients alive 23% belong to NYHA class I, 42% to II and 35% to III; none is in class IV. Negative predictors of survival were found to be preoperative NYHA class IV (P < 0.01), low-voltage electrocardiogram (ECG) (P < 0.01), ascites (P < 0.01), dyspnea at rest (P < 0.05) and hyperbilirubinemia (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)