RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

[Nutraceuticals: a useful tool for cardiologists to improve lipid profile?] / I nutraceutici: potenziale risorsa per il cardiologo nel controllo dei livelli lipidici.

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Treatment strategies include both lifestyle modification and pharmacological therapy. Statins are among the most effective agents to achieve optimal LDL-cholesterol levels, but, not infrequently, patients suffer from myalgia or other side effects. The proven or perceived intolerance to statins requires, therefore, alternative lipid-lowering strategies. In recent years, nutraceuticals have become extensively accepted, and a growing number of molecules with hypothetical cholesterol-lowering activity have been proposed, sometimes with no scientific evidence and/or no methodological accuracy, based only on the belief that these agents are "natural" and do not show side effects. Here, nutraceuticals with potential evidence-based hypolipidemic effect will be reviewed (red yeast rice, berberine, phytosterols) in order to discuss their role in lipid control, their potential risks and their future prospective in clinical cardiology.

Aortic stenosis severity assessment: how to match non-invasive to invasive metrics.

This article underscores the importance of the haemodynamic principles of the methods of measurement, as well as inherited limitations of each method, to adequately manage differing data between invasive and non-invasive tests.

Transcatheter aortic valve implantation in low ejection fraction/low transvalvular gradient patients: the rule of 40.

BACKGROUND: Several factors have been identified as predictors of events after transcatheter aortic valve implantation (TAVI) but the impact of left ventricular ejection fraction (LVEF) and mean transaortic gradient (MTG) is controversial. This multicenter study aimed to clarify the prognostic role of low LVEF and low MTG after TAVI. METHODS: From 2007 to 2012, 764 consecutive patients with severe symptomatic aortic valve stenosis underwent TAVI at participating hospitals. Patients were divided according to LVEF and MTG into four groups. RESULTS: Sixty-four patients had LVEF 40% or less and MTG less than 40 mmHg, 76 had LVEF 40% or less and MTG at least 40 mmHg, 163 had LVEF more than 40% and MTG less than 40 mmHg, 461 had LVEF more than 40% and MTG at least 40 mmHg. Two-year mortality was significantly higher in patients with low LVEF and low MTG, whereas it was similar in patients with low LVEF and high MTG, high LVEF and low MTG, and high LVEF and high MTG (51.3 vs. 22.4 vs. 23.3. vs. 25.5%, respectively; P = 0.001). These results were confirmed by multivariate analysis, as the combination of low LVEF and low MTG (both less than 40) was identified as the stronger mid-term mortality predictor (hazard ratio 2.4, confidence interval 95% 1.4-3.9; P = 0.001). CONCLUSION: At least one parameter between LVEF or MTG over 40 predicts a good prognosis for TAVI patients at mid-term follow-up, whereas those with both left ventricular dysfunction and low mean aortic pressure gradient are at high risk of all-cause death after TAVI.

Intermediate Clinical and Hemodynamic Outcomes After Transcatheter Aortic Valve Implantation.

BACKGROUND: Concerns still exist regarding long-term results and freedom from valve-related adverse events in transcatheter aortic valve implantation (TAVI). The aim of this single-center retrospective study was to assess intermediate-term (up to 5-year) clinical and hemodynamic outcomes in patients undergoing TAVI. METHODS: From 2007 through 2013, 338 consecutive patients underwent TAVI at our institution. Preoperative variables were defined according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE) definitions, and outcomes were reported according to the Valve Academic Research Consortium (VARC)-2 definitions. Multivariate logistic regression analysis was performed to identify independent predictors of mortality at follow-up. RESULTS: transfemoral (TF) and transapical (TA) TAVI were performed in 233 (69%) and 105 (31%) patients, respectively. All-cause 30-day mortality was 4.4%, with no differences between TA and TF procedures. Thirty-day cardiovascular death, stroke, and myocardial infarction were not different between groups. The acute kidney injury (AKI) rate was higher in the TA group (30.5% versus 11.2%; p < 0.001). Access-related complications were more frequent in the TF group (36.1% versus 11.4%; p < 0.001). Mean follow-up was 22.3 ± 17.8 months (range, 1-74 months). Overall survival rates at 1, 3, and 5 years were 85.5% ± 2.1%, 69.9% ± 3.2%, and 61% ± 4.3%, respectively. Independent predictors of all-cause mortality at follow-up were previous myocardial infarction (odds ratio [OR], 2.7), any grade of paravalvular leak (PVL) (OR, 2.5), and AKI (OR, 3.1). Mean gradient and effective orifice area at follow-up were 10.7 ± 12.0 mm Hg and 1.1 ± 0.9 cm(2)/m(2), respectively. CONCLUSIONS: Our data show that TAVI has good early and intermediate-term clinical and hemodynamic outcomes in high-risk or inoperable patients with severe symptomatic aortic valve stenosis. PVL of any grade has a significant impact on survival.

Comparison of balloon-expandable versus self-expandable valves for transcatheter aortic valve implantation in patients with low-gradient severe aortic stenosis and preserved left ventricular ejection fraction.

A relevant proportion of patients, classified as severe aortic stenosis on the basis of valve area ≤1 cm(2), have a mean transvalvular gradient ≤40 mm Hg, despite a preserved left ventricular ejection fraction (LGSAS). We assessed the clinical and hemodynamic impact of transcatheter aortic valve implantation in patients with symptomatic LGSAS at high risk for surgery or inoperable, according to the type of percutaneous valve implanted. Ninety-five patients received an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, California) and 51 received a Medtronic CoreValve (Medtronic, Inc., Minneapolis, Minnesota). The hemodynamic performance of the 2 valves was similar in term of final transvalvular gradients (10 mm Hg, p = 0.069). Early mortality rate was 7% and was not different between the 2 valves (p = 0.73). During follow-up, cardiovascular mortality rate was similar between groups, and valve type was not a predictor of outcome (p = 0.72). Estimated survival by Kaplan-Meier at 2 years was 70%. At multivariate analysis, life-threatening or major bleeding, postprocedural aortic insufficiency, and acute kidney injury were the major predictors of an adverse outcome. In patients with LGSAS treated by transcatheter aortic valve implantation, the use of balloon-expandable versus self-expandable valves resulted in similar hemodynamic, early, and long-term clinical outcomes.

Unravelling the (arte)fact of increased pacemaker rate with the Edwards SAPIEN 3 valve.

AIMS: Early data on the Edwards SAPIEN 3 valve (S3-THV) have shown low rates of paravalvular leaks and vascular complications but relatively high 30-day permanent pacemaker implantation (PPMI) rates. No direct comparisons on clinical outcomes including PPMI rates are available for the S3-THV and the Edwards SAPIEN XT (XT-THV). We aimed to compare the 30-day PPMI rates in patients treated with the two prostheses and to assess the interplay among valve type, depth of implantation and PPMI rate. METHODS AND RESULTS: Two hundred and nine patients treated by TAVI were considered. The S3-THV was associated with higher PPMI rates compared to the XT-THV, both overall and in subgroups matched for several predictors of PPMI. However, in the S3-THV group, 30-day PPMI was strictly associated with deep valve implantation, and PPMI risk of high-implanted S3-THVs was similar to that of the overall XT-THV matched group. No cases of significant paravalvular leak were observed in the S3-THV group. CONCLUSIONS: The S3-THV was associated with a higher incidence of PPMI compared to the XT-THV. In the S3-THV group, pacemaker implantation was strictly associated with deep valve implantation. An implantation technique involving higher initial placement of the central marker (from 0 to 3 mm above the base of the aortic cusps) and, as a consequence, higher final valve depth might help in preventing post-TAVI PPMI with the S3-THV, without affecting the risk of paravalvular leak.

Cardiac autonomic dysfunction in the early phase after left ventricular assist device implant: Implications for surgery and follow-up.

PURPOSE: In congestive heart failure (CHF) patients, a profound cardiac autonomic derangement, clinically expressed by reduced heart rate variability (HRV), is present and is related to the degree of ventricular dysfunction. Implantation of a left ventricular assist device (LVAD) can progressively improve HRV, associated with an increased circulatory output. Data from patients studied at different times after LVAD implantation are controversial. The aims of this study were to assess cardiac autonomic function in the early phases after axial-flow LVAD implantation, and to estimate the potential relevance of recent major surgical stress on the autonomic balance.
 METHODS: HRV (time-domain; 24-h Holter) was evaluated in 14 patients, 44.8 ± 25.8 days after beginning of Jarvik-2000 LVAD support; 47 advanced stage CHF, 24 cardiac surgery (CS) patients and 30 healthy subjects served as control groups. INCLUSION CRITERIA: sinus rhythm, stable clinical conditions, no diabetes or other known causes of HRV alteration.
 RESULTS: HRV was considerably reduced in LVAD patients in the early phases after device implantation in comparison to all control groups. A downgrading of HRV parameters was also present in CS controls. Circadian oscillations were highly depressed in LVAD and CHF patients, and slightly reduced in CS patients.
 CONCLUSIONS: In CHF patients supported by a continuous-flow LVAD, a profound cardiac dysautonomia is still evident in the first two months from the beginning of circulatory support; the degree of cardiac autonomic imbalance is even greater in comparison to advanced CHF patients. The recent surgical stress could be partly linked to these abnormalities.

Valve replacement for severe aortic stenosis with low transvalvular gradient and left ventricular ejection fraction exceeding 0.50.

BACKGROUND: Severe aortic stenosis with a low transvalvular gradient and preserved left ventricular ejection fraction (LVEF) is often misdiagnosed, leading to undertreatment of such patients with no clear indication for surgical intervention. This study investigated the outcome of aortic valve replacement (AVR) in patients with severe aortic stenosis and a low transvalvular gradient despite normal LVEF. METHODS: Between 1985 and 2008, we evaluated 73 patients who underwent AVR compared with 29 patients who did not. Overall, aortic valve area was 1.0 cm2 or smaller, LVEF was 0.50 or higher, and transvalvular gradient was 30 mm Hg or less. Multivariate and Cox analyses were used to compare these two groups according to AVR. RESULTS: Compared with controls, AVR patients were younger and with higher body mass index. Coronary artery bypass grafting was performed simultaneously in 38 AVR patients (52%). At follow-up (median, 42 months; interquartile range, 23 to 75 months), survival was longer in AVR patients. By Cox analysis, AVR remained a major predictor of lower mortality (hazard ratio, 0.237; 95% confidence interval, 0.119 to 0.470; p<0.0001). CONCLUSIONS: In patients with severe aortic stenosis and low transvalvular gradient despite a normal LVEF, AVR was associated with significant improvement in long-term survival and functional status and with a low operative mortality.