[Cardiomyopathy in a 22-year-old man with a long history of methamphetamine abuse]. / Kardiomyopathie bei einem 22-Jährigen mit langjährigem Methamphetaminkonsum.

This article presents the case of a 22-year-old male patient with cardiomyopathy associated with a long history of methamphetamine abuse. Echocardiography revealed a dilated cardiomyopathy with highly reduced systolic pump function and severe mitral valve regurgitation. Inotropic treatment and MitraClip® (Abbott Vascular, Santa Clara, CA, USA) implantation resulted in enhancement of hemodynamics. The rising prevalence of methamphetamine abuse should give reason to raise awareness for the diagnostic work-up and patient history particularly in cases of unexplained cardiomyopathy in young patients.

AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac contractility in unchallenged mice but is deleterious in pressure-overload.

The downregulation of ß-adrenergic receptors (ß-AR) and decreased cAMP-dependent protein kinase activity in failing hearts results in decreased phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal amplifier element of ß-adrenergic signaling, leading to increased protein phosphatase 1 activity and dephosphorylation of key phosphoproteins, including phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to ß-AR desensitization; therefore its modulation is a promising approach in heart failure treatment. Aim of our study was to assess the effects of adeno-associated virus serotype 9 (AAV9) - mediated cardiac-specific expression of constitutively active inhibitor-1 (I-1c) and to investigate whether I-1c is able to attenuate the development of heart failure in mice subjected to transverse aortic constriction (TAC). 6-8 week old C57BL/6 N wild-type mice were subjected to banding of the transverse aorta (TAC). Two days later 2.8 × 1012 AAV-9 vector particles harbouring I-1c cDNA under transcriptional control of a human troponin T-promoter (AAV9/I-1c) were intravenously injected into the tail vein of these mice (n=12). AAV9 containing a Renilla luciferase reporter (AAV9/hRluc) was used as a control vector (n=12). Echocardiographic analyses were performed weekly to evaluate cardiac morphology and function. 4 weeks after TAC pressure- volume measurements were performed and animals were sacrificed for histological and molecular analyses. Both groups exhibited progressive contractile dysfunction and myocardial remodeling. Surprisingly, echocardiographic assessment and histological analyses showed significantly increased left ventricular hypertrophy in AAV9/I-1c treated mice compared to AAV9/hRluc treated controls as well as reduced contractility. Pressure-volume loops revealed significantly impaired contractility after AAV9/I-1c treatment. At the molecular level, hearts of AAV9/I-1c treated TAC mice showed a hyperphosphorylation of the SR Ca2+-ATPase inhibitor phospholamban. In contrast, expression of AAV9/I-1c in unchallenged animals resulted in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility. Our data suggest that AAV9-mediated cardiac-specific overexpression of I-1c, previously associated with enhanced calcium cycling, improves cardiac contractile function in unchallenged animals but failed to protect against cardiac remodeling induced by hemodynamic stress questioning the use of I-1c as a potential strategy to treat heart failure in conditions with increased afterload.

Golf for the mature athlete.

Golf is a different sport from all others discussed in this issue in one important aspect: Almost all of its practitioners play more, rather than less, as they mature. A great many of them play better, too. This additional play and skill can be highly satisfying to the participants; however, it puts them at risk for a number of overuse syndromes directly caused by the motion requirements of golf. In addition, the repetitive nature of the activity can exacerbate pre-existing and age-related orthopedic pathology as well. There is no substitute for attention to the preplay aspects of golf (warm-up, flexibility, and strengthening).