Research Spotlight

Ailawadi, G., H. L. Chang, P. T. O’Gara, K. O’Sullivan, Y. J. Woo, J. J. DeRose, Jr., M. K. Parides, V. H. Thourani, S. Robichaud, A. M. Gillinov, W. C. Taddei-Peters, M. A. Miller, L. P. Perrault, R. L. Smith, L. Goldsmith, K. A. Horvath, K. Doud, K. Baio, A. C. Gelijns, A. J. Moskowitz, E. Bagiella, J. H. Alexander and A. Iribarne (2017). “Pneumonia after cardiac surgery: Experience of the national institutes of health/canadian institutes of health research cardiothoracic surgical trials network.” J Thorac Cardiovasc Surg 153(6): 1384-1391.

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RATIONALE: Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures. OBJECTIVES: To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes. METHODS: A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs 48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 +/- 1.95 days (bootstrap 95% CI, 10.31-16.58). CONCLUSIONS: Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.

Milojevic, M., S. J. Head, M. J. Mack, F. W. Mohr, M. C. Morice, K. D. Dawkins, D. R. Holmes, Jr., P. W. Serruys and A. P. Kappetein (2017). “Influence of practice patterns on outcome among countries enrolled in the syntax trial: 5-year results between percutaneous coronary intervention and coronary artery bypass graftingdagger.” Eur J Cardiothorac Surg: 2017 May [Epub ahead of print].

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OBJECTIVES: To examine differences among participating countries in baseline characteristics, clinical practice, medication strategies and outcomes of patients randomized to coronary artery bypass grafting and percutaneous coronary intervention in the SYNTAX trial. METHODS: In SYNTAX, centres in 18 different countries enrolled 1800 patients, of which 8 countries enrolled >/=80 patients, what was projected to be a large enough sample size to be included in the analysis. Baseline characteristics, practice patterns and clinical outcomes were compared between the USA ( n = 245), the UK ( n = 267), Italy ( n = 197), France ( n = 208), Germany ( n = 179), Netherlands ( n = 148), Belgium ( n = 91) and Hungary ( n = 83). The remaining patients from other participating countries were pooled together ( n = 382). RESULTS: Five-year results demonstrated significantly different outcomes between countries. After adjustment, percutaneous coronary intervention patients in France had lower rates of major adverse cardiac and cerebrovascular events [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.37-0.98], while the incidence of repeat revascularization was higher in Hungary (HR = 1.89, 95% CI 1.14-3.42). Coronary artery bypass grafting showed the lowest rate of repeat revascularization in the UK (HR = 0.32, 95% CI 0.12-0.85). There were numerous differences in the risk profile of patients between participating countries, as well as marked differences in surgical practice across countries in the use of blood cardioplegia (range 3.1-89.0%; P < 0.001), bilateral internal mammary artery usage (range 7.8-68.2%; P < 0.001) and off-pump procedures (range 3.9-44.4%; P < 0.001). Variation was also found for percutaneous coronary intervention in the number of implanted stents (range 4.0 +/- 2.3 to 6.1 +/- 2.6; P < 0.001) as well as for the entire stents length (range 69.0 +/- 45.1 to 124.1 +/- 60.9; P < 0.001). Remarkable differences were observed in the prescription of post-coronary artery bypass grafting medication in terms of acetylsalicylic acid (range 79.6-95.0%; P = 0.004), thienopyridine (6.8-31.1%; P < 0.001) and statins (41.3-89.1%; P < 0.001). CONCLUSIONS: Patient characteristics and clinical patterns are significantly different between countries, resulting in significantly different 5-year outcomes. This article presents specific data that can further improve outcomes in each country.

Rini, B. I., V. Gruenwald, E. Jonasch, M. N. Fishman, Y. Tomita, M. D. Michaelson, J. Tarazi, L. Cisar, S. Hariharan, A. H. Bair, B. Rosbrook and T. E. Hutson (2017). “Long-term duration of first-line axitinib treatment in advanced renal cell carcinoma.” Target Oncol 12(3): 333-340.

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OBJECTIVE: We conducted a retrospective analysis of two clinical trials in treatment-naive patients (n = 402) with advanced renal cell carcinoma (RCC) treated with axitinib. Our objective was to compare duration of treatment (DT) and clinical outcome in patients who achieved DT >18 months (longer DT) versus /=10% tumor shrinkage at first scan (74.8% vs. 55.3%; p = 0.0001) and maximum on-study tumor shrinkage was greater in longer-DT versus shorter-DT group (-51.8% vs. -22.1%; p < 0.0001). Median OS was 32.6 months in the overall population while in the patients with longer DT the median was not reached. Treatment-related adverse events (AEs) grade >/=3 were more frequent in longer-DT versus shorter-DT and included hypertension (25.7% vs. 18.8%), diarrhea (15.1% vs. 4.4%), and weight decrease (11.2% vs. 3.2%); however, these AEs decreased over time in both groups. Eastern Cooperative Oncology Group performance status 0, favorable hematology values, no bone or liver metastases, and baseline tumor burden below the overall median were associated with longer DT. CONCLUSIONS: Longer duration (>18 months) of axitinib treatment was associated with increased frequency of early tumor shrinkage, greater magnitude of tumor shrinkage, and a favorable OS.

Roberts, P. R., N. Clementy, F. Al Samadi, C. Garweg, J. L. Martinez-Sande, S. Iacopino, J. B. Johansen, X. V. Prat, R. Kowal, D. Klug, L. Mont, J. Steffel, S. Li, D. Van Osch and M. F. El-Chami (2017). “A leadless pacemaker in the real-world setting: The micra transcatheter pacing system post-approval registry.” Heart Rhythm: 2017 May [Epub ahead of print].

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BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high rates of implant success, and safety and efficacy objectives were achieved. Outside of the investigational setting, there are concerns, particularly over cardiac effusion and perforation, device dislodgement, infection, telemetry, and battery issues. OBJECTIVE: The acute performance of the Micra transcatheter pacemaker from a worldwide postapproval registry is reported. METHODS: The registry is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra in the postapproval setting. The safety end point was system- or procedure-related major complications at 30 days post implant. We compared the major complication rate with that of the 726 patients from the investigational study. Electrical performance was also characterized. RESULTS: The device was successfully implanted in 792 of 795 registry patients (99.6%) by 149 implanters at 96 centers in 20 countries. Through 30 days post implant, a total of 13 major complications occurred in 12 patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%-2.62%). Major complications included cardiac effusion/perforation (1, 0.13%), device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for baseline differences, the rate of major complications in the registry trended lower than the investigational trial (odds ratio, 0.59, 95% confidence interval, 0.27-1.27; P = .18). Early pacing capture thresholds were low and stable. CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complication through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement, and infection were low, reinforcing the positive results seen in the investigational study.

Packer, M., B. Pitt, J. L. Rouleau, K. Swedberg, D. L. DeMets and L. Fisher (2017). “Long-term effects of flosequinan on the morbidity and mortality of patients with severe chronic heart failure: Primary results of the profile trial after 24 years.” JACC Heart Fail 5(6): 399-407.

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OBJECTIVES: The purpose of this clinical trial was to evaluate the long-term effects of flosequinan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Flosequinan was the first oral vasodilator to be used in the clinic to augment the effects of digitalis, diuretics, and angiotensin-converting enzyme inhibitors in heart failure. However, the drug activated neurohormonal systems and exerted both positive inotropic and chronotropic effects, raising concerns about its safety during long-term use. METHODS: Following a run-in period designed to minimize the risk of tachycardia, we randomly assigned 2,354 patients in New York Heart Association functional class III to IV heart failure and with an ejection fraction