Paolo Ferrazzi

Colchicine Reduces Postoperative Atrial Fibrillation Results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) Atrial Fibrillation Substudy

Background— Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. Methods and Results— The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P =0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P =0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P =0.009). Side effects were similar in the study groups. Conclusion— Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay. Clinical Trial Registration— URL: . Unique identifier: [NCT00128427][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00128427&atom=%2Fcirculationaha%2F124%2F21%2F2290.atomBackground— Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. Methods and Results— The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P=0.009). Side effects were similar in the study groups. Conclusion— Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00128427.

Failure of transradial approach during coronary interventions : Anatomic considerations

The anatomy of the radial artery has yet to be systematically studied from the perspective of using it as a route for catheter access. We prospectively performed angiography of the arteries of the upper limb to delineate the anatomic features of the radial artery as a way to determine the feasibility of using it as a route for coronary intervention. We studied 2,211 consecutive patients submitted to transradial cardiac catheterization. In all patients, an angiography of the upper limb arteries was performed before and after procedure. Radial puncture was successful in 98.9% of patients. At angiography, anatomic variations of upper limb arteries were noted in 505 patients (22.8%) and included tortuous configurations (3.8%), stenosis (1.7%), hypoplasias (7.7%), radioulnar loop (0.8%), abnormal origin of the radial artery (8.3%), and lusoria subclavian artery (0.45%). Overall procedural success by transradial approach was 97.5%. Patients with anatomic variations of radial artery had a significantly lower puncture (96.2% vs 99.7%, P < 0.0001) and procedural (93.1% vs 98.8%, P < 0.0001) success. The procedure was successfully performed by radial approach in 98.8% of patients with tortuous configurations, 91.9% of radial stenosis, 93.9% of hypoplastic radial artery, 83.3% of radioulnar loop, 96.7% of radial axillary origin, and 60% of lusoria subclavian artery setting. Anatomic variations of the radial artery are not rare. However, they do not represent an important limitation in transradial approach if they are well documented previously.

A contemporary European experience with surgical septal myectomy in hypertrophic cardiomyopathy

Aims The recent American College of Cardiology and American Heart Association Guidelines on hypertrophic cardiomyopathy (HCM) have confirmed surgical myectomy as the gold standard for non-pharmacological treatment of obstructive HCM. However, during the last 15 years, an extensive use of alcohol septal ablation has led to the virtual extinction of myectomy programmes in several European countries. Therefore, many HCM candidates for myectomy in Europe cannot be offered the option of this procedure. The purpose of our study is to report the difficulties and results in developing a myectomy programme for HCM in a centre without previous experience with this procedure. Methods and results The clinical course is reported of 124 consecutive patients with obstructive HCM and heart failure symptoms who underwent myectomy at a single European centre between 1996 and 2010. The median follow-up was 20.3 months (inter-quartile range: 3.9–40.6 months). No patients were lost to follow-up. A cumulative incidence of HCM-related death after myectomy was 0.8, 3.3, and 11.2% at 1, 5, and 10 years, respectively, including one operative death (procedural mortality 0.8%). The left ventricular (LV) outflow gradient decreased from 95 ± 36 mmHg before surgery to 12 ± 6 mmHg at most recent evaluation (P < 0.001), with none of the patients having a significant residual LV outflow gradient. Of the 97 patients in New York Heart Association functional class III–IV before surgery, 93 (96%) were in class I–II at most recent evaluation (P < 0.001). Conclusion Our results show that the development of a myectomy programme at a centre without previous experience with this procedure is feasible and can lead to highly favourable clinical results.

Colchicine prevents early postoperative pericardial and pleural effusions.

BACKGROUND No preventive pharmacologic strategies have been proven efficacious for the prevention of postoperative effusions after cardiac surgery. Colchicine is safe and efficacious for the prevention of pericarditis. On this basis, we realized a substudy of the COPPS trial to assess the efficacy and safety of colchicine for the prevention of postoperative pericardial and pleural effusions. METHODS The COPPS is a multicenter, double-blind, randomized trial, where 360 consecutive patients (mean age 65.7 ± 12.3 years, 66% men), 180 in each treatment arm, were randomized on the third postoperative day to receive placebo or colchicine for 1 month (1.0 mg twice daily for the first day, followed by a maintenance dose of 0.5 mg twice daily in patients ≥70 kg, and halved doses for patients <70 kg). The incidence of postoperative effusions was evaluated in each study group. RESULTS Despite similar baseline features, colchicine significantly reduced the incidence of postoperative pericardial (12.8% vs 22.8%, P = .019, relative risk reduction 43.9%, no. of patients needed to treat 10) and pleural effusions (12.2% vs 25.6%, P = .002, relative risk reduction 52.3%, no. of patients needed to treat 8). The rate of side effects (only gastrointestinal intolerance) and drug withdrawal was similar in the study groups with a trend toward an increased rate of both events for colchicine. In multivariable analysis, female gender (hazard ratio 1.76, 95% CI 1.03-3.03, P = .040) and pleura incision (hazard ratio 2.58, 95% CI 1.53-4.53, P < .001) were risk factors for postoperative effusions. CONCLUSIONS Colchicine is safe and efficacious for the primary prevention of postoperative effusions after cardiac surgery.

Following an initial decline, glomerular filtration rate stabilizes in heart transplant patients on chronic cyclosporine.

We previously reported that heart transplant patients given cyclosporine for more than 2 years (short-term evaluation) had severe renal lesions and markedly reduced glomerular filtration rate and renal plasma flow (Kidney Int 40:243-250, 1991). We report the analysis of renal function in the same patients after 3 additional years of follow-up (long-term evaluation) while they continued to take cyclosporine. Since the previous evaluation, the dose of cyclosporine was adjusted to maintain stable trough levels and antihypertensive therapy was unchanged. The mean time-averaged dose of cyclosporine during the follow-up was 4.5 +/- 2.1 mg/kg/d. The systolic blood pressure at long-term evaluation (146 +/- 16 mm Hg) was increased (P < 0.05) compared with that at short-term evaluation (140 +/- 13 mm Hg), whereas diastolic blood pressure (long-term 91 +/- 9 mm Hg v short-term 88 +/- 9 mm Hg) and mean blood pressure (long-term 110 +/- 12 mm Hg v short-term 108 +/- 11 mm Hg) did not change significantly. Serum creatinine concentrations at long-term (1.7 +/- 0.3 mg/dL) and at short-term (1.7 +/- 0.4 mg/dL) evaluations were similar. At long-term evaluation the renal plasma flow (300 +/- 64 mL/min/1.73 m2) was not decreased compared with that at short-term evaluation (325 +/- 94 mL/min/1.73 m2), while the glomerular filtration rate increased significantly (43 +/- 15 mL/min/1.73 m2 v 36 +/- 8 mL/min/1.73 m2, respectively; P < 0.05). None of the patients became proteinuric after short-term evaluation; in those patients who were already proteinuric, urinary protein excretion did not increase over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary receptor regulation of renin release.

Cardiopulmonary receptors have been shown to modulate renin release in animals. However, their involvement in reflex control of renin in humans has never been unequivocally established. This report reviews data on the effects on plasma renin activity of maneuvers (lower body negative pressure and passive leg raising) that reduce and increase central venous pressure and cardiac diameter without affecting blood pressure and heart rate, thereby deactivating and stimulating cardiopulmonary receptors with little or no involvement of the arterial baroreceptors. In normotensive subjects, reduction in central venous pressure was accompanied by an increase in plasma renin activity that was similar to the increase observed during tilt that reduced central venous pressure to a similar extent. Conversely, an increase in central venous pressure was accompanied by a reduction in plasma renin activity. The increase in plasma renin activity that followed the reduction in central venous pressure was drastically attenuated in four patients who had undergone cardiac transplantation, along with other reflex effects (changes in forearm vascular resistance and plasma norepinephrine) of cardiopulmonary receptor manipulations. There was a modest reduction in the overall reflex changes in plasma renin activity in patients with mild to moderate essential hypertension compared with normotensive subjects. However, patients with essential hypertension and cardiac hypertrophy showed marked attenuation of all reflex influences of the cardiopulmonary receptors. In five subjects, therapeutic regression of this structural alteration was associated with a clear improvement in the cardiopulmonary reflex. Thus, in humans, cardiopulmonary receptors exert an important reflex control of renin release. This control (which is due in part to receptors located in the cardiac walls) is moderately affected by a mild to moderate blood pressure elevation but is markedly impaired when the elevation produces structural alterations in the heart. Preliminary evidence, however, suggests that the cardiopulmonary reflex may be improved by a reduction in cardiac hypertrophy.

Is heart transplantation for complex congenital heart disease a good option? A 25-year single centre experience

OBJECTIVES Heart transplantation (HTx) in patients with complex congenital heart disease (CHD) is a challenge because of structural anomalies and multiple previous procedures. We analysed our results in adult and paediatric patients to evaluate outcome and assess risk factors affecting mortality. METHODS Between 1985 and 2011, among 839 patients who underwent HTx, 85 received transplantation for end-stage CHD. Patients were divided into four age subgroups: <1 year (8 patients, Group I), 1-10 years (20 patients, Group II), 11-18 years (24 patients, Group III) and >18 years (33 patients, Group IV) and into two time periods: 1985-2000 (47 patients) and 2001-2011 (38 patients). Anatomical diagnoses were single-ventricle defect in 37 patients (44%) and two-ventricle defect in 48 patients (56%). Seventy-three patients (86%) had undergone one or more cardiac surgical procedures prior to HTx (mean 2.4 ± 0.9). Twenty-two of them were suffering from Fontan failure. Mean pulmonary artery pressure was 25.2 ± 14.2 mmHg. Mean transpulmonary gradient was 9.4 ± 6.9 mmHg. RESULTS Mean follow-up after HTx was 7.8 ± 6.8 years. Survival at 1 month was 37.7% in Group I, 85.8% in Group II, 96.8% in Group II and 98.4% in Group IV and was significantly worse in younger recipients. Overall 30-day mortality was 17.6%. Currently 56 patients (65.8%) are alive. Overall survival at 1, 5, 10 and 15 years is 83-, 73-, 67- and 58%, respectively. There were 14 late deaths. Univariate analysis found that risk factors for early and late death were those related to recipient illness, such as pre-transplant creatinine, intravenous inotropic drugs, intravenous diuretics, mechanical ventilation and presence of protein-losing enteropathy (PLE). Multivariate analysis for all events (early and late deaths) identified preoperative mechanical ventilation as an independent risk factor for mortality. Number of previous procedures did not influence survival. Previous Fontan procedure did not increase mortality. We documented the reversibility of PLE in survivors. CONCLUSIONS We demonstrated that heart transplantation for patients with CHD can be performed with the expectation of excellent results. Previous procedures, including the Fontan operation, do not reduce survival. Mortality is related to preoperative patient condition. We advocate early referral of complex CHD patients for transplant assessment and for inclusion in waiting lists before the detrimental effects of end-stage failure manifest themselves.

Aortic valve disease with severe ventricular dysfunction: Stentless valve for better recovery

BACKGROUND Stentless bioprostheses and homografts show better hemodynamic profiles compared with conventional stented bioprostheses and mechanical valves. Few data are available on stentless aortic valve implantation for patients with severe left ventricular dysfunction. The aim of this retrospective study was to assess the potential benefits of stentless aortic valve implantation for patients undergoing isolated aortic valve replacement with left ventricular ejection fraction < or = 35%. METHODS From November 1988 through March 2000, 53 patients (45 men and 8 women, aged 64.2 +/- 15.2 years) with a LVEF < or = 35% (mean EF, 28.7 +/- 5.4%) underwent isolated, primary aortic valve replacement for chronic aortic valve disease. Twenty patients received stentless aortic valves and 33 patients received conventional stented bioprostheses and mechanical valves. Predictive factors for LVEF recovery at echocardiographic follow-up (36.2 +/- 32.1 months) were analyzed by simple and multiple regression analysis. RESULTS There were no significant differences between groups in early and late mortality. Stentless aortic valve implantation required a longer aortic cross-clamp time (p = 0.037). The stentless aortic valve group showed a better LVEF recovery (p = 0.016). Stentless aortic valves had a larger indexed effective orifice area compared with conventional stented bioprostheses and mechanical valves (p < 0.0001). A smaller indexed effective orifice area (p = 0.0008), chronic obstructive pulmonary disease (p = 0.015), and implantation of a conventional stented bioprosthesis or mechanical valve (p = 0.016) were related to reduced LVEF recovery by univariate analysis. A larger indexed effective orifice area (p = 0.024) was an independent predictive factor for a better LVEF recovery by multivariate analysis. CONCLUSIONS Stentless aortic valve implantation for patients with severe left ventricular dysfunction, even if technically more demanding, is a safe procedure that warrants a larger indexed effective orifice area leading to an enhanced LVEF recovery.

Biochemical evaluation of vacuum-assisted venous drainage: a randomized, prospective study

Aims of the study: In this prospective, randomized study, we investigate the potential advantages of vacuum-assisted venous drainage (VAVD), compared to gravitational drainage (GD), in patients undergoing first-time coronary artery bypass graft (CABG) surgery, concerning biochemical markers of organ and blood cell damage. Materials and methods: Seventy-two consecutive patients were randomized into two groups [‘Vacuum’ (VAVD) n= 36; ‘Not vacuum’ (GD) n= 36]. VAVD was achieved using a wall vacuum source and with a suction regulator connected to the vent port of the hardshell venous reservoir. In the VAVD group, we used 28-French venous cannulas, and 36-French in the GD group. In the VAVD group, we measured arterial perfusion flow (APF) and the venous reservoir volume (VRV) with and without vacuum application just after starting extracorporeal circulation (ECC). Six blood samples were drawn at different times before, during and after ECC. Routine blood tests were performed to evaluate hemolysis, and hepatic and renal function. Results: The two groups were similar in terms of preoperative and operative characteristics. There were no significant differences in biochemical markers of organ function or hemolysis between the two groups. In the VAVD patients, platelet count was higher at 24 h after the end of the operation (VAVD 151.77± 50.28 μl versus Not vacuum 124.93± 41.60 μl, p= 0.028). With the narrower venous cannulas (28-French), only VAVD achieved a satisfactory APF (VAVD 2.35± 0.38 l/min/m2 versus GD 1.88± 0.27 l/min/m2, p= 0.002), with a larger VRV (VAVD 1091.67± 421 ml versus GD 808.33± 284.31 ml, p= 0.025). Conclusion: Vacuum-assisted venous drainage is a technique comparable to gravitational drainage with regard to hemolysis and organ perfusion. It allows better perfusion flow and heart decompression with smaller venous cannulas. This study suggests reduced platelet consumption with VAVD.

Rationale and design of the COlchicine for Prevention of the Post-pericardiotomy Syndrome and Post-operative Atrial Fibrillation (COPPS-2 trial): A randomized, placebo-controlled, multicenter study on the use of colchicine for the primary prevention of the postpericardiotomy syndrome, postoperative effusions, and postoperative atrial fibrillation

BACKGROUND The efficacy and safety of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS), postoperative effusions, and postoperative atrial fibrillation (POAF) remain uncertain. Although preliminary data from a single trial of colchicine given for 1 month postoperatively (COPPS trial) were promising, the results have not been confirmed in a large, multicenter trial. Moreover, in the COPPS trial, colchicine was given 3 days postoperatively. METHODS The COPPS-2 study is a multicenter, double-blind, placebo-controlled randomized trial. Forty-eight to 72 hours before planned cardiac surgery, 360 patients, 180 in each treatment arm, will be randomized to receive placebo or colchicine without a loading dose (0.5 mg twice a day for 1 month in patients weighing ≥70 kg and 0.5 mg once for patients weighing <70 kg or intolerant to the highest dose). The primary efficacy end point is the incidence of PPS, postoperative effusions, and POAF at 3 months after surgery. Secondary end points are the incidence of cardiac tamponade or need for pericardiocentesis or thoracentesis, PPS recurrence, disease-related admissions, stroke, and overall mortality. CONCLUSIONS The COPPS-2 trial will evaluate the use of colchicine for the primary prevention of PPS, postoperative effusions, and POAF, potentially providing stronger evidence to support the use of preoperative colchicine without a loading dose to prevent several postoperative complications. ClinicalTrials.gov Identifier: NCT01552187.