Massimiliano Mulè

Dual Antiplatelet Therapy Versus Aspirin Alone in Patients Undergoing Transcatheter Aortic Valve Implantation

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve implantation (TAVI), but this approach is not evidence based. The goal of the present study was to determine whether DAPT in patients undergoing TAVI is associated with improved outcomes compared to aspirin alone. From May 2009 to August 2010, consecutive patients were randomized to receive a 300-mg loading dose of clopidogrel on the day before TAVI followed by a 3-month maintenance daily dose of 75 mg plus aspirin 100 mg lifelong (DAPT group) or aspirin 100 mg alone (ASA group). The primary end point was the composite of major adverse cardiac and cerebrovascular events, defined as death from any cause, myocardial infarction, major stroke, urgent or emergency conversion to surgery, or life-threatening bleeding. The cumulative incidence of major adverse cardiac and cerebrovascular events at 30 days and 6 months was 14% and 16%, respectively. No significant differences between the DAPT and ASA groups were noted at both 30 days (13% vs 15%, p = 0.71) and 6 months (18% vs 15%; p = 0.85). In conclusion, the strategy of adding clopidogrel to aspirin for 3 months after TAVI was not found to be superior to aspirin alone. These results must be confirmed in a larger randomized trial.

Exercise stress echocardiography for the study of the pulmonary circulation.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19–62 yrs (mean 36 yrs). Mean pulmonary artery pressure (P̄pa) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of P̄pa–Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility α was calculated from each P̄pa–Q plot to estimate compliance. P̄pa increased from 14±3 mmHg to 30±7 mmHg, and decreased to 19±4 mmHg after 5 min recovery. The slope of P̄pa–Q was 1.37±0.65 mmHg·min−1·L−1 with an extrapolated pressure intercept of 8.2±3.6 mmHg and an α of 0.017±0.018 mmHg−1. These results agree with those of previous invasive studies. Multipoint P̄pa–Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.

Exercise Stress Echocardiography of the Pulmonary Circulation: Limits of Normal and Sex Differences

BACKGROUND Exercise stress echocardiography has not been recommended in the diagnostic workup of pulmonary hypertension because of insufficient certainty about feasibility and limits of normal. METHODS Doppler echocardiography pulmonary hemodynamic measurements were performed at a progressively increased workload in 56 healthy male and 57 healthy female volunteers aged 19 to 63 years. Mean pulmonary artery pressure (mPAP) was estimated from the maximal tricuspid regurgitation jet velocity. Cardiac index was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility a index, the percentage change of vessel diameter permm Hg of mPAP, was calculated from multipoint mPAP-cardiac output (CO) plots. RESULTS Peak exercise at 175 ±50 W was associated with an mPAP of 33±7 mm Hg and a CO of 18 ±5 L/min. The slope of mPAP-CO relationships was 1.5 ± 0.5 mm Hg/L/min, and the distensibility coefficient ( α ) was 1.3%± 1.0%/mm Hg. Maximal workload and cardiac index were higher in men than in women ( P , .05), but mPAP-cardiac index relationships were not different. However,women had a higher a (1.6%± 1.3%/mm Hg vs 1.1%± 0.6%/mm Hg, P < .05). The average mPAP-cardiac index slope was higher and a lower in subjects ≥50 years old. Upper limits of normal of mPAP at exercise were 34 mm Hg at a CO , 10 L/min, 45 mm Hg at a CO <20 L/min, and 52 mm Hg at a CO<30 L/min. These values are in keeping with previously reported invasive measurements. CONCLUSIONS Exercise stress echocardiography of the pulmonary circulation is feasible and allows for fl ow-corrected definition of upper limits of normal. Women have a more distensible pulmonary circulation.

Quality of life assessment after percutaneous aortic valve implantation

AIMS To assess the NYHA class and the quality of life (QoL) scores after percutaneous aortic valve implantation (PAVI) with the 18-Fr CoreValve prosthesis. METHODS AND RESULTS From April 2007 until August 2008, 57 consecutive patients with aortic stenosis were evaluated for PAVI. Of these, 30 patients with successfully prosthesis implantation had more than 5-month follow-up. QoL assessment was realized with the SF-12v2 Health-Survey, a simple questionnaire designed for self-administration that provides easily interpretable scales for physical [physical component summary (PCS)] and mental [mental component summary (MCS)] health. The questionnaire was administered before and 5 months after PAVI. All 30 patients had a marked upgrading in haemodynamic and echocardiographic parameters (peak-to-peak gradient from 64 +/- 23 to 2 +/- 0.4; P < 0.001; aortic valve area index from 0.3 +/- 0.1 to 0.9 +/- 0.3; P < 0.001), with an improvement in New York Heart Association (NYHA) class at discharge and after 5 months. Mean pre-operative SF-12v2 scores showed a severe impairment of perceived quality of life compared with general Italian population >75 years, both for physical (PCS-baseline 28.5 vs. 37.9, P < 0.001) and mental scores (MCS-baseline 37.8 vs. 45.4, P < 0.001). After 5 months, a striking improvement in both scores (PCS 41.3-MCS 48.3; P < 0.001) was observed. CONCLUSION Our preliminary results show a marked short-term improvement in functional status and physical and mental health in patients underwent PAVI.

Original ResearchPulmonary Vascular DiseaseExercise Stress Echocardiography of the Pulmonary Circulation: Limits of Normal and Sex Differences

BACKGROUND Exercise stress echocardiography has not been recommended in the diagnostic workup of pulmonary hypertension because of insufficient certainty about feasibility and limits of normal. METHODS Doppler echocardiography pulmonary hemodynamic measurements were performed at a progressively increased workload in 56 healthy male and 57 healthy female volunteers aged 19 to 63 years. Mean pulmonary artery pressure (mPAP) was estimated from the maximal tricuspid regurgitation jet velocity. Cardiac index was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility a index, the percentage change of vessel diameter permm Hg of mPAP, was calculated from multipoint mPAP-cardiac output (CO) plots. RESULTS Peak exercise at 175 ±50 W was associated with an mPAP of 33±7 mm Hg and a CO of 18 ±5 L/min. The slope of mPAP-CO relationships was 1.5 ± 0.5 mm Hg/L/min, and the distensibility coefficient ( α ) was 1.3%± 1.0%/mm Hg. Maximal workload and cardiac index were higher in men than in women ( P , .05), but mPAP-cardiac index relationships were not different. However,women had a higher a (1.6%± 1.3%/mm Hg vs 1.1%± 0.6%/mm Hg, P < .05). The average mPAP-cardiac index slope was higher and a lower in subjects ≥50 years old. Upper limits of normal of mPAP at exercise were 34 mm Hg at a CO , 10 L/min, 45 mm Hg at a CO <20 L/min, and 52 mm Hg at a CO<30 L/min. These values are in keeping with previously reported invasive measurements. CONCLUSIONS Exercise stress echocardiography of the pulmonary circulation is feasible and allows for fl ow-corrected definition of upper limits of normal. Women have a more distensible pulmonary circulation.

Comparison of Complications and Outcomes to One Year of Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis

Comparisons of transcatheter aortic valve implantation (TAVI) to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis remain sparse or limited by a short follow-up. We sought to evaluate early and midterm outcomes of consecutive patients (n = 618) undergoing successful TAVI (n = 218) or isolated SAVR (n = 400) at 2 centers. The primary end point was incidence of Valvular Academic Research Consortium-defined major adverse cerebrovascular and cardiac events (MACCEs) up to 1 year. Control of potential confounders was attempted with extensive statistical adjustment by covariates and/or propensity score. In-hospital MACCEs occurred in 73 patients (11.8%) and was more frequent in patients treated with SAVR compared to those treated with TAVI (7.8% vs 14.0%, p = 0.022). After addressing potential confounders using 3 methods of statistical adjustment, SAVR was consistently associated with a higher risk of MACCEs than TAVI, with estimates of relative risk ranging from 2.2 to 2.6 at 30 days, 2.3 to 2.5 at 6 months, and 2.0 to 2.2 at 12 months. This difference was driven by an adjusted increased risk of life-threatening bleeding at 6 and 12 months and stroke at 12 months with SAVR. Conversely, no differences in adjusted risk of death, stroke and myocardial infarction were noted between TAVI and SAVR at each time point. In conclusion, in a large observational registry with admitted potential for selection bias and residual confounding, TAVI was not associated with a higher risk of 1-year MACCEs compared to SAVR.

Management of implant failure during transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic stenosis. There is a paucity of detailed data on the management and outcome of complications related to the sub‐optimal deployment of the prosthesis. We appraised the incidence and management of early implant failure occurring during TAVI. Methods: Of 110 patients who underwent TAVI using the third generation 18‐French CoreValve ReValving System (Medtronic, MN) in our Institution between June 2007 and January 2010, we identified those experiencing early implant failure and reported on their management and clinical outcome. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular event (MACCE) at 30 days and mid‐term follow up. Results: Early implant failure occurred in 18 of 110 patients (16.3%). The most common cause was prosthesis under‐expansion conditioning moderate to severe peri‐valvular leak (44.4%). Prosthesis deployment too low or too high with respect to the aortic annulus leading to severe peri‐valvular leak occurred in 22.2% and 5.5% of patients, respectively. Need of valve retrieve after the first attempt of deployment occurred in four cases (22.2%). Prosthesis embolization in the ascending aorta occurred in 5.5% of patients who experienced early implant failure. All implant failure cases were managed percutaneously with gain in aortic valve area from 0.44 ± 0.17 to 1.28 ± 0.27 cm2 (P < 0.001), decrease of mean transaortic gradient from 55.00 ± 19.51 to 11.58 ± 5.91 mmHg (P < 0.001) and no MACCE at 30 days. After 11 ± 6 months, MACCE occurred cumulatively in two patients (11.1%). Conclusions: Early implant failure can complicate the TAVI procedure with the CoreValve system, but it can be managed safely and effectively with bailout transcatheter techniques, avoiding surgery, with good early and mid‐term clinical and echocardiographic results.

Exercise Pathophysiology in Patients With Chronic Mountain Sickness

BACKGROUND Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. METHODS Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. RESULTS The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). CONCLUSIONS The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

The valve-in-valve technique: Transcatheter treatment of aortic bioprothesis malposition

Percutaneous aortic valve replacement is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic valve stenosis. The impossibility of repositioning of the current transcatheter prosthesis in case of suboptimal placement is the main limit of these devices. Here, we report on a case of an 84‐year‐old woman successfully treated with implantation of two 18‐Fr CoreValve® prosthesis (CoreValve®, Irvine, California), because of the suboptimal deployment of the first one, analyzing the procedural technique and the immediate and short‐term clinical and hemodynamic results.

Postprocedural management of patients after transcatheter aortic valve implantation procedure with self‐expanding bioprosthesis

Background: Transcatheter aortic valve implantation (TAVI) carries higher risk of post‐procedural adverse events than conventional percutaneous cardiovascular interventions. We report our experience about postoperative management protocol adopted in our Division. Methods: One hundred and ten patients underwent TAVI and 108 were transferred to the cardiac intensive care unit (CICU) after procedure. During the first 48 hours, vital parameters were monitored continuously. Close attention was given to rhythm and atrio‐ventricular conduction disturbances, systemic blood pressure, fluid balance and vascular accesses. Results: The most common complications were renal impairment (21.3%), femoral artery pseudo‐aneurysms (FAP) (11%), new complete atrioventricular block (20.3 %), cerebral vascular accident (4.5%) and cardiac perforation due to temporary pacemaker lead (1.8%). Ultrasound‐guided compression repair was considered the first line treatment for FAP, but in 6 cases surgical treatment was immediately performed due to the rapid expansion of FAP. Complete atrio‐ventricular block occurred in 22 patients (20.3 %) within the first 24 hours after TAVI and a permanent pacemaker was implanted in 21 patients (19.1%). Acute kidney injury occurred in 18 patients (35%) with pre‐procedural chronic renal failure and in 5 patients (9%) without preoperative renal dysfunction. Conclusions: After TAVI, cardiovascular complications are common and therefore accurate standardized management of patients in CICU during the first 48 hours is mandatory to early detect and manage complications and to decrease the rate of adverse events and the length of in‐hospital stay.