In pressure overload-induced hypertrophy, the heart increases its reliance on glucose as a fuel while decreasing fatty acid oxidation. A key regulator of this substrate switching in the hypertrophied heart is peroxisome proliferator-activated receptor ␣ (PPAR␣). We tested the hypothesis that down-regulation of PPAR␣ is an essential component of cardiac hypertrophy at the levels of increased mass, gene expression, and metabolism by pharmacologically reactivating PPAR␣. Pressure overload (induced by constriction of the ascending aorta for 7 days in rats) resulted in cardiac hypertrophy, increased expression of fetal genes (atrial natriuretic factor and skeletal ␣-actin), decreased expression of PPAR␣ and PPAR␣-regulated genes (medium chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase 4), and caused substrate switching (measured ex vivo in the isolated working heart preparation). Treatment of rats with the specific PPAR␣ agonist WY-14,643 (8 days) did not affect the trophic response or atrial natriuretic factor induction to pressure overload. However, PPAR␣ activation blocked skeletal ␣-actin induction, reversed the down-regulation of measured PPAR␣-regulated genes in the hypertrophied heart, and prevented substrate switching. This PPAR␣ reactivation concomitantly resulted in severe depression of cardiac power and efficiency in the hypertrophied heart (measured ex vivo). Thus, PPAR␣ down-regulation is essential for the maintenance of contractile function of the hypertrophied heart.Pressure overload of the heart activates a complex series of interconnected signaling cascades resulting in adaptive responses for the maintenance of a normal cardiac output (1, 2). This adaptation includes alterations in cardiomyocyte mass (trophic response), gene expression, and metabolism (1-6). At the trophic level, the heart hypertrophies (1, 7). At the transcriptional level, the heart reexpresses fetal genes (such as atrial natriuretic factor (ANF) 1 and skeletal ␣-actin) while depressing the expression of various adult isoforms (e.g. cardiac ␣-actin) (4, 8). At the level of metabolism, the hypertrophied heart increases reliance on glucose as a fuel and depresses fatty acid oxidation (the dominant energy source for the normal heart) (5, 6, 9).A key regulator of substrate switching in the heart is postulated to be PPAR␣ (10). This nuclear receptor regulates the expression of several genes involved in both fatty acid and glucose oxidation. These include the fatty acid transporter (FAT/CD36), fatty acid-binding protein, malonyl-CoA decarboxylase, muscle-specific carnitine palmitoyltransferase I, medium and long chain acyl-CoA dehydrogenases, as well as pyruvate dehydrogenase kinase 4 (11-16). For example, increased fatty acids in the diabetic milieu result in activation of PPAR␣, induction of PPAR␣-regulated genes, and increased fatty acid oxidation with depression of glucose oxidation (17, 18). In contrast, increased reliance of the hypertrophied heart on glucose as a fuel is associated with decreased PPAR␣ expression and ...

Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, an important modulator of fatty acid oxidation. We hypothesized that increased fatty acid availability would increase the expression and activity of heart and skeletal muscle MCD, thereby promoting fatty acid utilization. The results show that high-fat feeding, fasting, and streptozotocin-induced diabetes all significantly increased the plasma concentration of nonesterified fatty acids, with a concomitant increase in both rat heart and skeletal muscle MCD mRNA. Upon refeeding of fasted animals, MCD expression returned to basal levels. Fatty acids are known to activate peroxisome proliferator-activated receptor-alpha (PPARalpha). Specific PPARalpha stimulation, through Wy-14643 treatment, significantly increased the expression of MCD in heart and skeletal muscle. Troglitazone, a specific PPARgamma agonist, decreased MCD expression. The sensitivity of MCD induction by fatty acids and Wy-14643 was soleus > extensor digitorum longus > heart. High plasma fatty acids consistently increased MCD activity only in solei, whereas MCD activity in the heart actually decreased with high-fat feeding. Pressure overload-induced cardiac hypertrophy, in which PPARalpha expression is decreased (and fatty acid oxidation is decreased), resulted in decreased MCD mRNA and activity, an effect that was dependent on fatty acids. The results suggest that fatty acids induce the expression of MCD in rat heart and skeletal muscle. Additional posttranscriptional mechanisms regulating MCD activity appear to exist.

The authors report the first emergent angiographic assessment of the coronaries with accompanying echocardiography in a 64-year-old man with dermatomyositis, who presented with ST segment elevation and cardiac specific enzyme derangements highly suggestive of myocardial infarction in the presence of acute pancreatitis. Both studies revealed no anatomical or functional evidence of obstructive coronary disease. Although the mechanism of electrocardiogram abnormalities found in acute pancreatitis remains to be elucidated fully, the authors propose a direct cardiac toxic effect by the pancreatic proteolytic enzymes to account for these changes and we recommend an angiographic approach as the first step to avoid the potentially lethal administration of thrombolytic therapy or potent anticoagulation.

Reports of cases of heart failure due to vitamin B1 deficiency in this country are still scanty enough to justify the publication of a single case. This one was made more interesting by being due, apparently, to a pure dietary deficiency, unconditioned by alcoholism or gastro-intestinal disease.

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Atrial Fibrillation (AFib) ablation volume and its relation to outcomes posit negatively for low volume centers, the ideal annual hospital volume is 50. Fifty four in-patients have been followed. The primary outcome is the change in an AFib validated outcomes questionnaire that subjects completed pre-procedure, 6 months, 1 year, and annually thereafter. Secondary endpoints included duration of maintaining normal sinus rhythm (NSR) and adverse events. At 6 months, the overall questionnaire score improved by 30 points from the baseline score (95% CI: (16, 43), p < 0.001). The improvement from baseline was also maintained at 1 year, with the 1-year change score of 22 points (95% CI: (14, 30), p < 0.001), additionally significant improvements were observed in each of the subscales. Based on a Kaplan-Meier analysis, 96% of subjects maintained NSR at 6 months, 87% maintained NSR at 1 year, and 78% maintained NSR at 2 years. Epicardial and endocardial ablation for AF care is feasible in a low-volume ablation hospital with careful long-term tracking. Patients can receive quality care closer to home and not incur costs associated with traveling for health care-a determinate of value- based care.

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