Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is an important cause of heart failure-related disability over a wide range of ages. Profiles of severe progressive heart failure symptoms and death, or heart transplantation deserve more complete definition within large patient cohorts. METHODS AND RESULTS: Clinical and morphological features of heart failure were assessed in 293 consecutive HCM patients over a median follow-up of 6 (inter-quartile range 2-11) years. Gross and histopathological features were analysed in 12 patients for whom the heart was available for inspection. Of the 293 patients, 50 (17%) developed severe progressive heart failure, including 18 who died or were transplanted. Three profiles of heart failure were identified predominantly associated with: (i) end-stage systolic dysfunction (ejection fraction <50%) (15; 30%); (ii) left ventricular (LV) outflow obstruction at rest (11; 22%); and (iii) non-obstructive with preserved systolic function (24; 48%). Overall, atrial fibrillation (AF) contributed to heart failure in 32 patients (64%) among the three profiles. Compared with other patients, those non-obstructive with preserved systolic function had earlier onset of heart failure symptoms mainly due to diastolic dysfunction, and the most accelerated progression to advanced heart failure and adverse outcome (P = 0.04). Thrombi were identified in the left atrial appendage of five gross heart specimens all belonging to patients with AF, including three of which were unrecognized clinically and had previously embolized. Extensive myocardial scarring with LV remodelling was evident in all end-stage patients; no or only focal scars were present in other patients. CONCLUSION: Profiles of advanced heart failure in HCM are due to diverse pathophysiological mechanisms, including LV outflow obstruction and diastolic or global systolic ventricular dysfunction. Atrial fibrillation proved to be the most common disease variable associated with progressive heart failure. Recognition of the heterogeneous pathophysiology of heart failure in HCM is relevant, given the targeted management strategies necessary in this disease.

Effect of combustion-derived particles on genotoxicity and telomere length: A study on human cells and exposed populations.

Particulate matter (PM) from combustion processes has been associated with oxidative stress to DNA, whereas effects related to telomere dysfunction are less investigated. We collected air-borne PM from a passenger cabin of a diesel-propelled train and at a training facility for smoke diving exercises. Effects on oxidative stress biomarkers, genotoxicity measured by the comet assay and telomere length in PM-exposed A549 cells were compared with the genotoxicity and telomere length in peripheral blood mononuclear cells (PBMCs) from human volunteers exposed to the same aerosol source. Although elevated levels of DNA strand breaks and oxidatively damaged DNA in terms of Fpg-sensitive sites were observed in PBMCs from exposed humans, the PM collected at same locations did not cause genotoxicity in the comet assay in A549 cells. Nevertheless, A549 cells displayed telomere length shortening after four weeks exposure to PM. This is in line with slightly shorter telomere length in PBMCs from exposed humans, although it was not statistically significant. In conclusion, the results indicate that genotoxic potency measured by the comet assay of PM in A549 cells may not predict genotoxicity in exposed humans, whereas telomere length measurements may be a novel indicator of genotoxic stress in cell cultures and humans.