Aliased Flow Signal Planimetry by Cardiovascular Magnetic Resonance Imaging for Grading Aortic Stenosis Severity: A Prospective Pilot Study.

Objectives: Transthoracic echocardiography (TTE) is the standard technique for assessing aortic stenosis (AS), with effective orifice area (EOA) recommended for grading severity. EOA is operator-dependent, influenced by a number of pitfalls and requires multiple measurements introducing independent and random sources of error. We tested the diagnostic accuracy and precision of aliased orifice area planimetry (AOAcmr), a new, simple, non-invasive technique for grading of AS severity by low-VENC phase-contrast cardiovascular magnetic resonance (CMR) imaging. Methods: Twenty-two consecutive patients with mild, moderate, or severe AS and six age- and sex-matched healthy controls had TTE and CMR examinations on the same day. We performed analysis of agreement and correlation among (i) AOAcmr; (ii) geometric orifice area (GOAcmr) by direct CMR planimetry; (iii) EOAecho by TTE-continuity equation; and (iv) the "gold standard" multimodality EOA (EOAhybrid) obtained by substituting CMR LVOT area into Doppler continuity equation. Results: There was excellent pairwise positive linear correlation among AOAcmr, EOAhybrid, GOAcmr, and EOAecho (p < 0.001); AOAcmr had the highest correlation with EOAhybrid (R 2 = 0.985, p < 0.001). There was good agreement between methods, with the lowest bias (0.019) for the comparison between AOAcmr and EOAhybrid. AOAcmr yielded excellent intra- and inter-rater reliability (intraclass correlation coefficient: 0.997 and 0.998, respectively). Conclusions: Aliased orifice area planimetry by 2D phase contrast imaging is a simple, reproducible, accurate "one-stop shop" CMR method for grading AS, potentially useful when echocardiographic severity assessment is inconclusive or discordant. Larger studies are warranted to confirm and validate these promising preliminary results.

Grading of aortic stenosis severity: a head-to-head comparison between cardiac magnetic resonance imaging and echocardiography.

AIM: To prospectively evaluate the accuracy of cardiac magnetic resonance (cMR) imaging for the assessment of aortic valve effective orifice area (EOA) by continuity equation and anatomical aortic valve area (AVA) by direct planimetry, as compared with transthoracic (TTE) and transesophageal (TEE) two-dimensional (2D) echocardiography, respectively. METHODS AND RESULTS: A total of 31 patients (21 men, 10 women, mean age 69 ± 10 years) with moderate-to-severe aortic stenosis (AS) diagnosed by TTE and scheduled for elective aortic valve replacement, underwent both cMR and TEE. AVA by cMR was obtained from balanced steady-state free-precession cine-images. EOA was computed from phase-contrast MR flow analysis. AVA at cMR (0.93 ± 0.42 cm2) was highly correlated with TEE-derived planimetry (0.92 ± 0.32 cm2) (concordance correlation coefficient, CCC = 0.85). By excluding 11 patients with extensively thickened and heavily calcified cusps, the CCC increased to 0.93. EOA at cMR (0.86 ± 0.30 cm2) showed a strong correlation with TTE-derived EOA (0.78 ± 0.25 cm2) (CCC = 0.82). CONCLUSIONS: cMR imaging is an accurate alternative for the grading of AS severity. Its use may be recommended especially in patients with poor transthoracic acoustic windows and/or in case of discordance between 2D echocardiographic parameters.

Psychotropic drugs and ventricular repolarisation: The effects on QT interval, T-peak to T-end interval and QT dispersion.

OBJECTIVE: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death. METHODS: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval. RESULTS: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12.66 (95% confidence interval (CI), 3.9-41.1), p<0.001), an effect independent from action on QT interval. Mood stabilisers showed significant effects on ventricular repolarisation: lithium was associated with a TpTe prolongation (OR=2.12 (95% CI, 1.12-4), p=0.02), while valproic acid with a TpTe reduction (OR=0.6 (95% CI, 0.37-0.98), p=0.04). Among antipsychotics, clozapine increased TpTe (OR=9.5 (95% CI, 2.24-40.39), p=0.002) and piperazine phenothiazines increased QT dispersion (OR=2.73 (95% CI, 1.06-7.02), p=0.037). CONCLUSIONS: Treatment with psychotropic drugs influences TpTe and QT dispersion. These parameters might be considered to better estimate the sudden cardiac death risk related to specific medications. Beyond antipsychotics and antidepressants, mood stabilisers determine significant effects on ventricular repolarisation.

Inflammation and thrombosis - testing the hypothesis with anti-inflammatory drug trials.

The hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammation-related plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.

Proton pump inhibitors and clopidogrel: an association to avoid?

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastro-intestinal bleeding often leads to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising concerns about the cardiovascular safety of this drug combination. Clinical trials investigating PPI-clopidogrel interactions have provided conflicting results and are all subject to methodological critiques. The much desired and much needed prospective, double-bind, randomized, placebo-controlled trials with adequate follow-up and sample size have not yet been performed. Indeed, the Clopidogrel and the Optimization of GI Events Trial, which would have had such characteristics, was stopped prematurely. As a consequence, the question of the PPI-clopidogrel interaction is still unresolved, and clinical consequences cannot be excluded. At this time such combination therapy should, therefore, be provisionally advocated only for patients at high risk of bleeding (prior upper gastro-intestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection) and avoiding PPIs with strong affinity for cytochrome CYP2C19, such as omeprazole and esomeprazole.

[Proton pump inhibitors and clopidogrel: an association to avoid?]. / Inibitori di pompa protonica e clopidogrel: un'associazione da evitare?

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastrointestinal bleeding often leads clinicians to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising doubts on the safety of this drug combination. Clinical trials investigating PPI-clopidogrel interaction have provided conflicting results and have been often criticized. Moreover, a prospective, double-bind, randomized, placebo-controlled study conducted with adequate follow-up and sample size has not yet been performed. Indeed, the COGENT trial, which would have had such characteristics, has been stopped prematurely. The question is therefore still unresolved, and clinical effects of PPI-clopidogrel interaction cannot be excluded. As a practical consequence, this combination therapy is recommended only for patients at high risk of bleeding (prior upper gastrointestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection), avoiding in any case PPIs with greater affinity for CYP2C19, such as omeprazole and esomeprazole.

Non-invasive in vivo detection of peripheral limb ischemia improvement in the rat after adipose tissue-derived stromal cell transplantation.

BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) might help repair ischemic cardiovascular tissue. Their in vivo effects on the bioenergetics and microcirculation of ischemic muscle through a variety of non-invasive techniques was examined. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in 42 rats. One day after femoral artery ligation, 6 rats per group were randomly injected with intramuscularly allogeneic ADSCs (10(6)-10(7)-10(8) cells/ml), conditioned media from ADSC cultures (conditioned media [CM], control), saline (control), allogeneic fibroblasts (10(7) cells/ml, control) or a non-conditioned medium (control). Rats underwent magnetic resonance angiography (MRA), short-time inversion recovery (STIR) edema-weighed imaging, proton MR spectroscopy ((1)H-MRS), thermal infrared imaging (IRI), immunoblotting and immunofluorescence analysis on both hindlimbs for 4 weeks. MRA and STIR documented arterial occlusion and ischemia, respectively. Muscle (1)H-MRS and IRI showed reductions of total creatine (tCr)/water and skin temperature in occluded hind limbs, respectively. At 4 weeks, the ADSC and CM groups had greater recovery of skin temperature and tCr/water in ischemic limbs compared with controls (P<0.01), with increased expression of α-sarcomeric actinin and vascular growth factors, such as hepatocyte growth factor (HGF), increased vessel density (capillaries, arterioles and venules) and less type III collagen. CONCLUSIONS: Allogeneic ADSCs improve ischemic muscle metabolism, increase neovasculogenesis and decrease fibrosis, largely through a paracrine mechanism. (1)H-MRS and IRI are useful tools to monitor attempts at salvaging the ischemic tissues with cell-derived novel therapies.