Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin.

AIMS: Systemic inflammation and increased activity of atrial NOX2-containing NADPH oxidases have been associated with the new onset of atrial fibrillation (AF) after cardiac surgery. In addition to lowering LDL-cholesterol, statins exert rapid anti-inflammatory and antioxidant effects, the clinical significance of which remains controversial. METHODS AND RESULTS: We first assessed the impact of cardiac surgery and cardiopulmonary bypass (CPB) on atrial nitroso-redox balance by measuring NO synthase (NOS) and GTP cyclohydrolase-1 (GCH-1) activity, biopterin content, and superoxide production in paired samples of the right atrial appendage obtained before (PRE) and after CPB and reperfusion (POST) in 116 patients. The effect of perioperative treatment with atorvastatin (80 mg once daily) on these parameters, blood biomarkers, and the post-operative atrial effective refractory period (AERP) was then evaluated in a randomized, double-blind, placebo-controlled study in 80 patients undergoing cardiac surgery on CPB. CPB and reperfusion led to a significant increase in atrial superoxide production (74% CI 71-76%, n = 46 paired samples, P < 0.0001) and a reduction in atrial tetrahydrobiopterin (BH4) (34% CI 33-35%, n = 36 paired samples, P < 0.01), and in GCH-1 (56% CI 55-58%, n = 26 paired samples, P < 0.001) and NOS activity (58% CI 52-67%, n = 20 paired samples, P < 0.001). Perioperative atorvastatin treatment prevented the effect of CPB and reperfusion on all parameters but had no significant effect on the postoperative right AERP, troponin release, or NT-proBNP after cardiac surgery. CONCLUSION: Perioperative statin therapy prevents post-reperfusion atrial nitroso-redox imbalance in patients undergoing on-pump cardiac surgery but has no significant impact on postoperative atrial refractoriness, perioperative myocardial injury, or markers of postoperative LV function. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01780740.

Does furosemide prevent renal dysfunction in high-risk cardiac surgical patients? Results of a double-blinded prospective randomised trial.

OBJECTIVE: Renal dysfunction following cardiac surgery is more apparent in high-risk patients with pre-existing renal dysfunction, diabetes and impaired left-ventricular function, and following complicated procedures involving prolonged cardiopulmonary bypass (CPB). The aim of this prospectively randomised double-blinded placebo-controlled study was to evaluate reno-protective effect of low-dose furosemide infusion in this high-risk group. METHODS: Patients with preoperative serum creatinine >130 micromol/l (1.4 mg/dl), left-ventricular ejection fraction <50%, congestive heart failure, diabetes, or procedures involving prolonged CPB were randomised to receive either saline at 2 ml/h (n=21), or furosemide at 4 mg/h (n=21). Infusion was commenced after induction of anaesthesia and continued for 12h postoperatively. Renal dysfunction was defined as >50% increase in serum creatinine postoperatively, or >130 micromol/l (1.4 mg/dl), or requirement for haemodialysis, or all of these. In patients with preoperative serum creatinine >130 micromol/l, >50% increase over preoperative levels was used to define postoperative renal dysfunction. RESULTS: Following cardiac surgery, patients receiving furosemide had a higher urine output (3.4+/-1.2 ml/kg/h in furosemide group and 1.2+/-0.5 ml/kg/h in placebo group; p<0.001), higher postoperative fluid requirement (4631+/-1359 ml in furosemide group and 3714+/-807 ml in placebo group, p=0.011), and lower urinary-creatinine (2+/-1.3 micromol/l in furosemide group and 5.9+/-2.5 micromol/l in placebo group p<0.001). Both groups had significant increase in retinol binding protein/creatinine ratio (7.2+/-6 to 3152+/-1411 in furosemide group; 4.9+/-2.1 to 2809+/-1125 in placebo group; p<0.001) and peak serum creatinine (98+/-33 to 177+/-123 micromol/l in furosemide group; 96+/-20 to 143+/-87 micromol/l in placebo group; p<0.001), and a significant decrease in peak creatinine-clearance (64.3+/-29.4 to 39.1+/-16.6 ml/min in furosemide group; 65.5+/-38.6 to 41.8+/-17.8 ml/min in placebo group; p<0.001) following cardiac surgery, implying significant renal injury following cardiac surgery. Peak creatinine levels (177+/-123 micromol/l in furosemide group and 143+/-87 micromol/l in placebo group; p=0.35) and peak creatinine-clearance (39.1+/-16.6 ml/min in furosemide group and 41.8+/-17.8 ml/min in placebo group; p=0.61) were similar in the two groups. Importantly, there was no difference in incidence of renal dysfunction between the furosemide group (9/21) and the control group (8/21) (relative risk 1.1, 95% confidence interval 0.6-2.2; p=0.99). CONCLUSIONS: Our randomised trial did not demonstrate any benefit of furosemide-infusion postoperatively in high-risk cardiac surgical patients. Although urinary output increased with furosemide, there was no decrease in renal injury, and no decrease in incidence of renal dysfunction.

Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase.

Atrial fibrillation (AF) is a growing public health burden, and its treatment remains a challenge. AF leads to electrical remodeling of the atria, which in turn promotes AF maintenance and resistance to treatment. Although remodeling has long been a therapeutic target in AF, its causes remain poorly understood. We show that atrial-specific up-regulation of microRNA-31 (miR-31) in goat and human AF depletes neuronal nitric oxide synthase (nNOS) by accelerating mRNA decay and alters nNOS subcellular localization by repressing dystrophin translation. By shortening action potential duration and abolishing rate-dependent adaptation of the action potential duration, miR-31 overexpression and/or disruption of nNOS signaling recapitulates features of AF-induced remodeling and significantly increases AF inducibility in mice in vivo. By contrast, silencing miR-31 in atrial myocytes from patients with AF restores dystrophin and nNOS and normalizes action potential duration and its rate dependency. These findings identify atrial-specific up-regulation of miR-31 in human AF as a key mechanism causing atrial dystrophin and nNOS depletion, which in turn contributes to the atrial phenotype begetting this arrhythmia. miR-31 may therefore represent a potential therapeutic target in AF.

3f prosthesis aortic cusp replacement: implantation technique and early results.

Stentless aortic bioprostheses have been successfully used for over a decade. The 3f bioprosthesis is a new equine pericardial stentless valve, unique in its tubular design, preserving the native aortic sinuses post-implant. Forty-six consecutive aortic valve replacements with the 3f bioprosthesis were performed between June 2003 and January 2005. The patients were prospectively assessed and echocardiography was performed at 6 months, 12 months, and annually thereafter. The median follow-up was 2.1 + or - 0.9 years. There was one early and 4 late deaths; none were valve-related. The 2-year mean transvalvular gradient was 8.8 + or - 3.8 mm Hg, the mean echocardiographic aortic regurgitation grade was 0.4 + or - 0.7 (grade 1 being trivial). Echocardiographic sizing of the aortic annulus before surgery accurately predicted prosthesis size. The 3f bioprosthesis is easy to implant. Early clinical results are favorable, with hemodynamic profiles consistent with those of other stentless prostheses. Longer follow-up is required to confirm its durability.

Superior vena cava reconstruction with homograft conduit under circulatory arrest.

Superior vena cava obstruction may be due to benign or malignant causes. This may be treated surgically by using autologous saphenous vein grafts, autologous pericardial patches cut and reconstituted as tubes, expanded polytetrafluoroethylene grafts, or percutaneously by balloon dilatation and stenting procedures. We report a case of superior vena cava obstruction in which the obstructed segment was bypassed using a tube constructed from aortic and pulmonary homograft conduits, under hypothermic circulatory arrest without using jugulo-atrial shunts, leaving the obstructed segment in situ.

Cardiopulmonary bypass and renal injury.

Renal dysfunction following cardiopulmonary bypass (CPB) is well recognized. The extent of perioperative renal impairment ranges from subclinical injury to established renal failure requiring dialysis. Its incidence varies considerably, depending on the definition and criteria used in the different studies. Acute renal failure (ARF) affects 1-5% of patients and remains a major cause of morbidity and mortality. Co-morbidities, including diabetes mellitus, impaired left ventricular function and advanced age, are recognized predisposing factors. The pathophysiology is multifactorial and is thought related to the systemic inflammatory response and renal hypoperfusion secondary to extracorporeal circulation. Non-pulsatile flow during CPB is thought to be an important aetiological factor, resulting in renal vasoconstriction and ischaemic renal injury. A theoretical reduction in the incidence and severity of postoperative renal impairment has been proposed by advocating the use of pulsatile flow during CPB, or eliminating CPB, especially in high-risk patients. The current evidence, however, is conflicting. Several large observational studies, including a large proportion of high-risk patients, have demonstrated a significant reduction in the frequency of renal failure in patients undergoing off-pump surgery. As older, sicker patients increasingly constitute the cardiac surgical population, the incidence of postoperative renal injury is likely to increase. Further studies addressing various renoprotective strategies in higher-risk patients are awaited.

Recurrent localized fibrous tumor of the pleura.

Localized fibrous tumors of the pleura are rare. They are often asymptomatic and may have symptoms based on size, bronchial invasion, or hormone production, or a combination of these. Complete resection offers the best chance of cure. However, recurrence is reported in a significant number of patients and can often be treated by repeated resection, albeit with increasing difficulty. We present a case in which delayed recurrence occurred after excision of such a tumor. This required a chest-wall resection and reconstruction after which a second recurrence occurred. Further thoracotomy including a latissimus dorsi free flap procedure was needed for a third-time recurrence.

Transsternal thymectomy for myasthenia gravis: surgical outcome.

BACKGROUND: Transsternal thymectomy is well established in the treatment of myasthenia gravis. Surgical strategy and patient selection, however, remain controversial. This paper reports the experience of a supraregional center looking into the influence of different preoperative risk factors on surgical outcome. METHODS: Between 1987 and 1998, 85 consecutive patients (65 female; mean age, 30.5 years) were enrolled. The mean preoperative Myasthenia Gravis Foundation of America stage was 2.3. The preoperative, early, and late follow-up data were analyzed retrospectively. RESULTS: Mean follow-up was 4.5 years (range, 1 to 14; 376 follow-up years). Mean duration of disease before surgery was 31 months. There were no operative or late deaths. Eight patients had major complications. Seventy-two patients were free from any early or late morbidity. Immunosupression therapy patients were more prone to have complications. At their last visit, 15 patients (17%) were in complete remission; 67 reported clinical improvement. Sixty-three were asymptomatic or in stage I on no or minimal treatment. Remission and clinical improvement were not predicted by patient's age, sex, duration of disease prior to surgery, thymic pathology, or antiacetylcholine receptor antibodies titer. Greater severity of symptoms before surgery was associated with greater subsequent improvement. Remission at 1 year predicted remission at the end of follow-up. CONCLUSIONS: Transsternal thymectomy for myasthenia gravis is safe and effective. It benefits most patients, especially those with severe symptoms. The long interval from diagnosis to surgery demonstrates it is never too late for thymectomy.