Restrictive cardiomyopathy and pseudoxanthoma elasticum skin lesions.

: We report a rare case of a patient with AL amyloidosis and pseudoxanthoma elasticum skin lesions. An association between these two diseases has been previously described as amyloid elastosis in only six cases, but cardiac findings were not fully elucidated. The peculiarity of our case is that a severe cardiac involvement influenced the prognosis negatively. Furthermore, the electron microscopic examination did not show all the peculiar histopathological findings of amyloid elastosis, precluding a final diagnosis of this disease.

Eligibility for the Subcutaneous Implantable Cardioverter-Defibrillator in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: High-risk hypertrophic cardiomyopathy (HCM) patients benefit from the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) may provide comparable protection while avoiding the shortcomings of transvenous (TV) leads. We assessed S-ICD eligibility according to surface ECG screening test in a cohort of high-risk HCM patients. METHODS AND RESULTS: 47 HCM patients (3 S-ICD candidates; 41 TV-ICD patients without pacing indication; and 3 pacemaker-dependent TV-ICD patients) underwent 4 screening protocols: standard (n = 44); exercise (n = 33); continuous pacing (n = 44); alternating paced/spontaneous QRS (n = 41). Of the 44 patients in the standard screening group, 41 (93%) were eligible. Max LV thickness was inversely related to the number of qualifying leads (3 leads: 21 ± 4 mm; 2 leads: 22 ± 6 mm; 1 lead: 25 ± 6 mm; no leads: 28 ± 11 mm; P = 0.07). Of the 33 patients in the exercise group, 5 were ineligible (3 after exercise). Of these, 2 became eligible after moving sternal electrodes from the left to the right parasternal line (eligibility rate: 30/33; 91%). Of the 44 patients in the continuous pacing group, 28 (64%) were eligible, 8 of which with right parasternal electrodes. In the paced/spontaneous QRS group (n = 41), 21 patients (51%) had at least 1 eligible lead during pacing and retained compatibility on the same lead during spontaneous rhythm, 5 of which with right parasternal electrodes. CONCLUSIONS: S-ICD screening failure is low in HCM, provided that patients with severe hypertrophy are carefully evaluated. Exercise test should be performed and right parasternal leads tested. Pacemaker patients display lower eligibility rate.

Patterns of left ventricular longitudinal strain and strain rate in Olympic athletes.

BACKGROUND: Two-dimensional speckle-tracking echocardiography is an emerging modality for the assessment of systolic and diastolic myocardial deformation in a broad variety of clinical scenarios. However, normal values and physiologic limits of left ventricular strain and strain rate in trained athletes are largely undefined. METHODS: Two hundred consecutive Olympic athletes (grouped into skill, power, mixed, and endurance disciplines) and 50 untrained controls were evaluated by two-dimensional speckle-tracking echocardiography. Left ventricular global systolic longitudinal strain (GLS), systolic strain rate, early diastolic strain rate (SRE) and late diastolic strain rate (SRA) were calculated. RESULTS: GLS was normal, although mildly lower, in athletes compared with controls (-18.1 ± 2.2% vs -19.4 ± 2.3%, P < .001), without differences related to type of sport. Systolic strain rate was also lower in athletes (-1.00 ± 0.15 vs -1.11 ± 0.15 sec(-1), P < .001), with the lowest value in endurance disciplines (-0.96 ± 0.13 sec(-1), P < .001). No difference existed for SRE (1.45 ± 0.32 vs 1.51 ± 0.35 sec(-1), P = .277), while SRA was lower in athletes (0.67 ± 0.25 vs 0.81 ± 0.20 sec(-1), P < .001). Both SRE (1.37 ± 0.30 sec(-1), P < .001) and SRA (0.62 ± 0.23 sec(-1), P < .001) showed the lowest values in endurance disciplines. The fifth and 95th percentiles calculated as reference values in athletes were as follows: for GLS, -15% and -22%; for systolic strain rate, -0.8 and -1.2 sec(-1); for SRE, 1.00 and 2.00 sec(-1); and for SRA, 0.30 and 1.20 sec(-1). CONCLUSION: The present study shows that highly trained athletes have normal GLS and strain rate parameters of the left ventricle, despite mild differences compared with untrained controls. These data may be implemented as reference values for the clinical assessment of the athletes and to support the diagnosis of physiologic cardiac adaptations in borderline cases.

Contribution of genome-wide association studies to scientific research: a pragmatic approach to evaluate their impact.

The factual value of genome-wide association studies (GWAS) for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125) of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies). As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a pragmatic approach that helps interpret and exploit GWAS knowledge.