Sabet W. Hashim

Noncardiogenic pulmonary edema after cardiopulmonary bypass. An anaphylactic reaction to fresh frozen plasma.

Nine episodes of fulminant noncardiogenic pulmonary edema after cardiopulmonary bypass were observed in eight patients between September 1977 and December 1982. All these catastrophic reactions occurred during administration of fresh frozen plasma 30 minutes to 6 hours after discontinuation of cardiopulmonary bypass. In one patient, two episodes of noncardiogenic pulmonary edema occurred 4 hours apart. In each instance, fresh frozen plasma was being administered. In all patients, pulmonary artery diastolic pressure became elevated during the administration of fresh frozen plasma while left atrial pressure or pulmonary capillary wedge pressure progressively decreased, and cardiac output deteriorated markedly in all but one patient. Corticosteroids, positive end-expiratory pressure, and catecholamines were administered to all patients. All deaths were due to a decrease in cardiac output. Cardiac output did not increase substantially with the use of an intraaortic balloon pump or the administration of catecholamines. The last two patients in the series showed a steady and remarkable improvement in cardiac output when the wedge pressure was increased to a level above 15 mm Hg with the administration of normal saline solution. Our data suggest the following: (1) noncardiogenic pulmonary edema after cardiopulmonary bypass is most probably an anaphylactic reaction to fresh frozen plasma. (2) The syndrome is reversible within hours; in only one patient (who suffered noncardiogenic pulmonary edema twice) did adult respiratory distress syndrome develop. (3) The three deaths were not related to hypoxia but to the deleterious effects of low cardiac output associated with hypovolemia secondary to fluid loss through the lungs and possibly across other capillary beds. Therefore, treatment should include restoration of adequate left-sided filling pressures to achieve satisfactory cardiac output.

Modulation of Transforming Growth Factor-β Signaling and Extracellular Matrix Production in Myxomatous Mitral Valves by Angiotensin II Receptor Blockers

Background— Little is known about the pathophysiology of myxomatous degeneration of the mitral valve, the pathological hallmark of mitral valve prolapse, associated with symptomatic mitral regurgitation, heart failure, and death. Excess transforming growth factor (TGF)-&bgr; signaling is known to cause mitral valve degeneration and regurgitation in a mouse model of Marfan syndrome. We examined if TGF-&bgr; signaling is dysregulated in clinical specimens of sporadic mitral valve prolapse compared with explanted nondiseased mitral valves and we tested the effects of angiotensin II receptor blockers on TGF-&bgr; signaling in cultured human mitral valve cells. Methods and Results— Operative specimens, cultured valve tissues, and cultured valvular interstitial cells were obtained from patients with mitral valve prolapse undergoing mitral valve repair or from organ donors without mitral valve disease. Increased extracellular matrix in diseased valve tissue correlated with an upregulation of TGF-&bgr; expression and signaling as evidenced by SMAD2/3 phosphorylation. Both TGF-&bgr; ligand and signaling mediators colocalized primarily to valvular interstitial cells suggesting autocrine/paracrine activation. In cultured valve tissue, exogenous TGF-&bgr; increased basal extracellular matrix production, whereas serological neutralization of TGF-&bgr; inhibited disease-driven extracellular matrix overproduction. TGF-&bgr;-induced extracellular matrix production in cultured valvular interstitial cells was dependent on SMAD2/3 and p38 signaling and was inhibited by angiotensin II receptor blockers. Conclusions— TGF-&bgr; has a profibrotic role in the pathogenesis of sporadic mitral valve prolapse. Attenuation of TGF-&bgr; signaling by angiotensin II receptor blockers may represent a mechanistically based strategy to modulate the pathological progression of mitral valve prolapse in patients.

Preoperative proteinuria predicts acute kidney injury in patients undergoing cardiac surgery

OBJECTIVE The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. METHODS The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (≤ 1.1 mg/mmol), 11 to 29 mg/g (1.2-3.3 mg/mmol), 30 to 299 mg/g (3.4-33.8 mg/mmol), and 300 mg/g or greater (≥ 33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase ≥ 50% or ≥ 0.3 mg/dL; 26.5 μmol/L). RESULTS An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m(2) or greater. CONCLUSIONS Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery.

Optimal methods of repair of descending thoracic aortic transections and aneurysms

The method for optimal protection of the spinal cord and viscera during surgical repair of aneurysms and acute disruptions of the descending thoracic aorta is controversial. We reviewed our experience with 50 consecutive patients who underwent such repairs between January 1968 and April 1982 to determine the safest method of protection. Thirty-two had acute transections, 9 had ruptured aneurysms, 6 had false aneurysms, and three had atherosclerotic aneurysms. Extracorporeal circulation was used in 21 patients with an average cross-clamp time of 67 minutes, a Gott shunt was used in 26 with an average cross-clamp time of 74 minutes, and no shunt was used in 3 patients with cross-clamp times of 20, 24, and 50 minutes. Paraplegia was significantly reduced with both extracorporeal circulation and the heparin-bonded Gott shunt; however, the former method was associated with a high incidence of postoperative bleeding in conjunction with systemic heparinization, and this, in turn, contributed to a high mortality, particularly in patients with traumatic transection who often had associated severe injuries. We believe that the Gott shunt provides the best protection, particularly in the setting of a training program where a relatively small number of these operations are performed and cross-clamp times may be prolonged.

Combined valve replacement and myocardial revascularization

Combining valve replacement with coronary artery bypass (CABG) for significant concomitant disease remains a controversial subject. To determine the operative results following combined valve replacement and CABG, we evaluated 201 patients seen consecutively between July 1977 and June 1982. CABG for vessels with greater than 70% stenosis was performed with aortic valve replacement in 106 patients, with mitral valve replacement in 82, and with aortic and mitral valve replacement in 13. There were 143 men and 58 women; the mean age was 67 years. Nine operative deaths (8.5%) occurred with aortic valve replacement and CABG: 5 of 25 (20%) when cardioplegia was not used and 4 of 81 (4.9%) with cardioplegia (p less than 0.01). The operative mortality rate for isolated aortic valve replacement without coronary disease during the same period was 5.9% (10 of 168). The late actuarial survival rate is similar for aortic valve replacement alone or aortic valve replacement and CABG. There were no operative deaths among patients having undergone aortic and mitral valve replacement and CABG; the rate was 15% (9 of 60) in patients having undergone aortic and mitral replacement and CABG. The operative mortality rate was 21.9% for mitral valve replacement and CABG (18 of 82). Rheumatic disease was present in 14 of these patients, two of whom had early deaths (14.3%), both after repeat mitral operations; 11 mitral valve replacements and CABG were done for degenerative mitral regurgitation with no deaths, and the remaining 57 patients had ischemic mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of central somatosensory conduction time in patients undergoing cardiopulmonary bypass: An index of neurologic function

It is feasible to monitor somatosensory evoked potentials and central somatosensory conduction times during open heart surgery and cardiopulmonary bypass with moderate or profound hypothermia. Central conduction times are reproducible, have acceptably low interpatient and intrapatient variability, and are not significantly affected by fentanyl-induced anesthesia. There is a predictable logarithmic relationship between central conduction times and temperature with the central conduction time increasing by 6.6 percent for a 1 degree C decrease in temperature. These data indicate that somatosensory conduction times may be a useful index of central nervous system integrity during open heart surgery that utilizes cardiopulmonary bypass and hypothermia.

Outcomes for Mitral Valve Surgery Among Medicare Fee-for-Service Beneficiaries, 1999 to 2008

Background— Mitral valve surgery in older adults carries with it substantial morbidity and mortality risks, yet there are a paucity of national surveillance data. Therefore, we sought to determine trends in hospitalization rate, readmission, and mortality among Medicare fee-for-service (FFS) patients undergoing mitral valve surgery. Methods and Results— Inpatient Medicare standard analytic files were used to identify 100% of FFS patients aged ≥65 years who underwent mitral valve surgery between 1999 and 2008. We constructed a denominator file from Medicare administrative data to report hospitalization rates for mitral valve surgery (total and isolated) per 100 000 beneficiary-years. For isolated mitral valve surgery, 30-day readmission, 30-day mortality, and 1-year mortality outcomes were ascertained through corresponding inpatient and vital status files, and risk-standardized rates were calculated adjusting for age, sex, race, and comorbidities. During 1999 to 2008, the overall rate of mitral valve surgery per 100K beneficiary-years declined (56/100K to 51/100K), and the proportion of patients undergoing mitral valve repair (versus replacement) increased (24.7% to 46.9%, P<0.001). For isolated mitral valve surgery, there were significant declines in risk-adjusted 30-day mortality (8.1% to 4.2%, P<0.001 for trend) and 1-year mortality (15.3% to 9.2%, P=0.003 for trend) and a slight decline in risk-adjusted 30-day readmission (23.0% to 21.0%, P=0.035 for trend) over the study period. Mortality rates decreased in all age, sex, and race subgroups, and among patients undergoing mitral valve repair or replacement, but remained higher among patients aged ≥85 years, women, and nonwhites. Conclusions— Between 1999 and 2008, outcomes after isolated mitral valve surgery significantly improved among Medicare FFS patients. Disparities among demographic subgroups indicate potential areas for quality improvement.

Pseudoprolapse of the anterior leaflet in chronic ischemic mitral regurgitation: Identification and repair

OBJECTIVE Recurrence rates as high as 30% have been observed 6 months after treatment of chronic ischemic mitral regurgitation (CIMR) with isolated annuloplasty. We postulated that the high early recurrence rates resulted from the presence of untreated pseudoprolapse of the anterior leaflet. METHODS We conducted a retrospective study of all mitral valve repairs for CIMR performed by a single surgeon (S.W.H.) from 1995 to 2011. After annuloplasty, Gore-Tex neochordae were added if the high-pressure saline test indicated the presence of pseudoprolapse of the anterior leaflet. RESULTS A total of 47 patients underwent mitral valve repair for CIMR. Of the 47 patients, 24 (51%) were found to have pseudoprolapse requiring the addition of neochordae. For all patients, the average age was 65.1 years, and 65.2% were men. Fourteen (30%) had had a preoperative intra-aortic balloon pump placed by cardiologists. Fourteen (30%) had severe pulmonary hypertension. Concomitant coronary artery bypass grafting was performed in 40 patients, with an average of 2.2 grafts; 7 had previously undergone coronary artery bypass grafting. Mitral Carpentier-Edwards physio annuloplasty rings were used in all patients with a mean size of 29 mm. One patient died postoperatively. Follow-up data were available for all 47 patients at an average of 4.9 years. The 5-year survival rate was 82.5%. The mean pre- and postoperative New York Heart Association class, ejection fraction, and mitral regurgitation grade were 3 and 1.52 (P < .0001), 34% and 41% (P = .0006), and 3.51 and 1.08 (P < .0001), respectively. Two patients developed greater than moderate mitral regurgitation. CONCLUSIONS Effective repair of CIMR should include surgical techniques to correct pseudoprolapse of the anterior leaflet, when present. The selective addition of Gore-Tex neochordae to an undersized annuloplasty nearly eliminates recurrent regurgitation after mitral valve repair for CIMR.

National Trends in Hospital Readmission Rates among Medicare Fee-for-Service Survivors of Mitral Valve Surgery, 1999–2010

Background Older patients who undergo mitral valve surgery (MVS) have high 1-year survival rates, but little is known about the experience of survivors. Our objective was to determine trends in 1-year hospital readmission rates and length of stay (LOS) in these individuals. Methods We included 100% of Medicare Fee-for-Service patients ≥65 years of age who underwent MVS between 1999–2010 and survived to 1 year (N = 146,877). We used proportional hazards regression to analyze the post-MVS 1-year readmission rate in each year, mean hospital LOS (after index admission), and readmission rates by subgroups (age, sex, race). Results The 1-year survival rate among patients undergoing MVS was 81.3%. Among survivors, 49.1% experienced a hospital readmission within 1 year. The post-MVS 1-year readmission rate declined from 1999–2010 (49.5% to 46.9%, P<0.01), and mean hospital LOS decreased from 6.2 to 5.3 (P<0.01). Readmission rates were highest in oldest patients, but declined in all age subgroups (65–74: 47.4% to 44.4%; 75–84: 51.4% to 49.2%, ≥85: 56.4% to 50.0%, all P<0.01). There were declines in women and men (women: 51.7% to 50.8%, P<0.01; men: 46.9% to 43.0%, P<0.01), and in whites and patients of other race, but not in blacks (whites: 49.0% to 46.2%, P<0.01; other: 55.0% to 48.9%, P<0.01; blacks: 58.1% to 59.0%, P = 0.18). Conclusions Among older adults surviving MVS to 1 year, slightly fewer than half experience a hospital readmission. There has been a modest decline in both the readmission rate and LOS over time, with worse outcomes in women and blacks.

Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury

The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05) and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05). Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb) in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL), during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01). Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.