An evidence-based strategy to screen for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Clinical practice guidelines recommend screening all systemic sclerosis (SSc) patients for pulmonary arterial hypertension (PAH) with yearly echocardiograms. There is a paucity of evidence to support these guidelines. RESEARCH QUESTION: Can a prediction model identify SSc patients with a very low probability of PAH and therefore not requiring annual screening echocardiogram? STUDY DESIGN AND METHODS: We performed a case-control study of 925 unselected SSc subjects nested in a multi-centered, longitudinal cohort. The probability of PAH for each subject was calculated using the results of multivariate logistic regression models. A cut-off was identified for the estimated probability of PAH below which no subject developed PAH (100% sensitivity). RESULTS: Study subjects were predominantly female (87.5%), with mean (SD) age 58.6 (11.7) years and disease duration of 18.2 (12.2) years. Thirty-seven subjects developed PAH during 5407.97 person-years of observation (incidence rate 0.68 per 100 person-years). Shortness of breath (SOB), diffusing capacity for carbon monoxide (DLCO) and NT-proBNP were independent predictors of PAH. All SSc-PAH cases had a probability of PAH of >1.1%. Subjects below this cut-off, none of whom had PAH, accounted for 46.2% of the study population. INTERPRETATION: A simple prediction model identified subjects at very low probability of PAH who could potentially forego annual screening echocardiogram. This represents almost half of SSc subjects in a general SSc population. This study, which is the first evidence-based study for the rational use of follow-up echocardiograms in an unselected SSc cohort, requires validation. The scoring system is freely available online at http://pahtool.ladydavis.ca.

Absence of cardiotoxicity with prolonged treatment and large accumulating doses of pegylated liposomal doxorubicin.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is used as a second-line therapy for gynecologic cancers, with a better short-term toxicity profile compared to doxorubicin or other anthracyclines. METHODS: We screened 14 patients with recurrent gynecologic cancers, who underwent prolonged treatment with large cumulative doses of PLD for overt or subtle signs of cardiotoxicity (CTX) using standard and advanced echocardiography techniques [3D volumetric method for left ventricular ejection fraction (LVEF) and left ventricular/right ventricular global longitudinal strain]. Half the patients had previous echocardiographic studies available for comparison. RESULTS: The average PLD treatment duration was 23.6 ± 10.8 months (range 13-57), accumulating dose of 1387 ± 483 mg (range 780-2538 mg). The study group had a normal LVEF both by 2D-echo (60 ± 5%, range 50-67) and 3D echo (58 ± 5%, range 46-63). Two patients (14%) were found to have minimally reduced ejection fraction by 2D and 3D echo (50%/46% and 51%/49%, respectively) that did not meet the current definition of CTX. For the seven patients who had consecutive echocardiography studies, the average LVEF remained stable between studies (59 ± 7, 60 ± 9 and 58 ± 10.5% for the latest study, previous, p < 0.79, and most remote study p < 0.9); No change was found in average left ventricular/right ventricular global longitudinal strain as well: -20.8 ± 4.6% at the latest study and -19.3 ± 2.6% for the previous (p < 0.51). CONCLUSION: No prevalent or incident cases of cardiotoxicity were found despite prolonged treatment with large cumulative doses of PLD, adding to previous reports on shorter treatment duration.

Design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

BACKGROUND: Mechanistic insights from 3D echocardiography (echo) can guide therapy. In particular, ischemic mitral regurgitation (MR) is difficult to repair, often persisting despite annular reduction. We hypothesized that (1) in a chronic infarct model of progressive MR, regurgitation parallels 3D changes in the geometry of mitral leaflet attachments, causing increased leaflet tethering and restricting closure; therefore, (2) MR can be reduced by restoring tethering geometry toward normal, using a new ventricular remodeling approach based on 3D echo findings. METHODS AND RESULTS: We studied 10 sheep by 3D echo just after circumflex marginal ligation and 8 weeks later. MR, at first absent, became moderate as the left ventricle (LV) dilated and the papillary muscles shifted posteriorly and mediolaterally, increasing the leaflet tethering distance from papillary muscle tips to the anterior mitral annulus (P<0.0001). To counteract these shifts, the LV was remodeled by plication of the infarct region to reduce myocardial bulging, without muscle excision or cardiopulmonary bypass. Immediately and up to 2 months after plication, MR was reduced to trace-to-mild as tethering distance was decreased (P<0.0001). LV ejection fraction, global LV end-systolic volume, and mitral annular area were relatively unchanged. By multiple regression, the only independent predictor of MR was tethering distance (r(2)=0.81). CONCLUSIONS: Ischemic MR in this model relates strongly to changes in 3D mitral leaflet attachment geometry. These insights from quantitative 3D echo allowed us to design an effective LV remodeling approach to reduce MR by relieving tethering.

Systemic immune reactions to HMG-CoA reductase inhibitors. Report of 4 cases and review of the literature.

Four patients with systemic autoimmune disorders, 3 of a serious nature, presented to 1 cardiologist over a 20-month span. In 3 of these cases, an HMG-CoA reductase inhibitor was presumably etiologic, while in the fourth case, the HMG-CoA reductase inhibitor might have unmasked the disorder. It would be useful to determine the true frequency of this complication, particularly in older patients not included in most of the statin trials to date. It is well established that autoimmune phenomena and particularly the development of autoantibodies increase with age. The data presented in this report that the group of HMG-CoA reductase inhibitors could be a heretofore poorly recognized etiologic agent. This issue might be addressed by a case-control study looking at the prevalence of statin use in elderly patients with systemic autoimmune disorders and in controls. Until then, the authors advise caution in the use of this class of medications in patient subgroups for whom no clear-cut clinical benefit has yet been proven.