Outcomes of volume-overloaded cardiovascular patients treated with ultrafiltration.

BACKGROUND: Ultrafiltration (UF) can rapidly and predictably remove extracellular and intravascular fluid volume. To date, assessment of UF in patients with cardiovascular disease has been confined to short- and medium-term studies in patients with a principal diagnosis of acute heart failure. METHODS: In-hospital and long-term outcomes were reviewed from consecutive patients with cardiovascular disorders and recognized pulmonary and systemic volume overload treated with a simplified UF system with the capability for peripheral venovenous access. Trained abstractors reviewed both paper and electronic medical records. Patients with a principal diagnosis of heart failure versus other primary hospital discharge diagnoses were identified according to International Classification of Diseases, 9th Revision standards by independent coders. RESULTS: For a period of 43 months, 100 patients (76 male/24 female, 65 +/- 14.0 years of age, systolic dysfunction 64%) were treated with UF during 130 hospitalizations. Baseline systolic blood pressure was 119 +/- 23 mm Hg. Before UF, 53% were receiving intravenous vasoactive therapy. By using UF, 7.1 +/- 3.9 L of ultrafiltrate were removed during 2.0 +/- 1.2 treatments per hospitalization. Baseline creatinine was 1.8 +/- 0.8 and 1.9 +/- 1.2 (not significant) at discharge. Of the 15 in-hospital deaths, 14 occurred during the initial hospitalization. Left ventricular dysfunction was related to 13 (87%) of the 15 deaths; no deaths were related to UF use. In hospitalizations with a principal diagnosis of heart failure (n = 79), in-hospital mortality was 7.6% compared with an ADHERE risk tree estimated mortality of 7.5%. Multivariate logistic regression identified a trend for decreased systolic blood pressure to predict patient initial hospitalization mortality (P = .06). Kaplan-Meier survivals for all patients were 71% at 1 year and 67% at 2 years. Cox regression found decreased systolic blood pressure as a predictor of long-term mortality (P = .025). Total volume of ultrafiltrate removed, ejection fraction, history of coronary artery disease, creatinine clearance, gender, age, and principal diagnosis of heart failure were not significantly associated with long-term mortality. CONCLUSION: This series extends the spectrum of patients previously reported to be treated with UF. Despite marked volume overload, UF-treated patients with a principal diagnosis of heart failure had inpatient outcomes similar to the ADHERE registry. UF should be considered for a broad range of patients who present with volume overload.

Thromboembolism is linked to intraventricular flow stasis in a patient supported with a left ventricle assist device.

A case report is presented of a left ventricular assist device (LVAD) recipient with a pre-existing thrombus that was removed on LVAD implant but quickly reformed and was removed, reformed again, and ultimately embolized, causing death. The thrombus formed proximal to the left ventricular outflow tract, because of the presence and subsequent repair of a calcified left ventricular infarct which had extruded from the septum. This region is vulnerable to flow stasis during LVAD support as predicted by experimental fluid mechanics studies, because of the lack of opening of the aortic valve. The presence of the repair and the altered flow field contributed to blood stasis and thrombus growth in a positive feedback loop. Although LVADs provide tremendous benefits for patients by reducing the symptoms of heart failure, the accompanying changes have some secondary consequences that remain problematic. One of these is an abnormal intraventricular flow field that decreases washout, especially in the region proximal to the left ventricular outflow tract, which is an area of flow stasis.

Clinical strategies and outcomes in advanced heart failure patients older than 70 years of age receiving the HeartMate II left ventricular assist device: a community hospital experience.

OBJECTIVES: The primary objective of this study was to determine outcomes in left ventricular assist device (LVAD) patients older than age 70 years. BACKGROUND: Food and Drug Administration approval of the HeartMate II (Thoratec Corporation, Pleasanton, California) LVAD for destination therapy has provided an attractive option for older patients with advanced heart failure. METHODS: Fifty-five patients received the HeartMate II LVAD between October 5, 2005, and January 1, 2010, as part of either the bridge to transplantation or destination therapy trials at a community hospital. Patients were divided into 2 age groups: ≥ 70 years of age (n = 30) and < 70 years of age (n = 25). Outcome measures including survival, length of hospital stay, adverse events, and quality of life were compared between the 2 groups. RESULTS: Pre-operatively, all patients were in New York Heart Association functional class IV refractory to maximal medical therapy. Kaplan-Meier survival for patients ≥ 70 years of age (97% at 1 month, 75% at 1 year, and 70% at 2 years) was not statistically different from patients <7 0 years of age (96% 1 month, 72% at 1 year, and 65% at 2 years, p = 0.806). Average length of hospital stay for the ≥ 70-year age group was 24 ± 15 days, similar to that of the < 70-year age group (23 ± 14 days, p = 0.805). There were no differences in the incidence of adverse events between the 2 groups. Quality of life and functional status improved significantly in both groups. CONCLUSIONS: The LVAD patients ≥ 70 years of age have good functional recovery, survival, and quality of life at 2 years. Advanced age should not be used as an independent contraindication when selecting a patient for LVAD therapy at experienced centers.

Aortic valve closure associated with HeartMate left ventricular device support: technical considerations and long-term results.

BACKGROUND: Aortic valve integrity is crucial for optimal left ventricular assist device (LVAD) support. Pre-existing native aortic insufficiency, aortic valve incompetence acquired during support, as well as previously placed prosthetic aortic valves present unique problems for these patients. METHODS: We reviewed and analyzed data for 28 patients who underwent left ventricular outflow tract closure associated with HeartMate I (n =12) and HeartMate II (n = 16) LVAD insertion or exchange. Indications for valve closure, surgical technique, LVAD function, survival rates and complications were retrospectively analyzed. Survival rates were compared with those of HeartMate LVAD patients (n = 104) who did not undergo aortic valve closure. RESULTS: Indications for closure included native aortic valve insufficiency (10 patients), aortic valve deterioration after prolonged LVAD support (8 patients) and previously placed mechanical (9 patients) or bioprosthetic aortic prostheses (1 patient). There were 2 operative and 5 late deaths (mean 227 days post-operatively). Of the deaths, none were due to aortic valve closure. Actuarial survival was 78% at 1 year and 53% at 3 years, which was statistically better than for our patients with an intact aortic outflow (61% at 1 year, 45% at 3 years; p < 0.05). Five patients had transplants, 1 patient was successfully bridged to recovery, and 15 patients remain on LVAD support. No patient with outflow closure developed regurgitation, embolization or compromised LVAD support. CONCLUSION: Outflow tract closure in LVAD-supported patients is safe, often necessary and well tolerated.

HeartMate left ventricular assist system exchange: results and technical considerations.

The duration times of left ventricular assist system (LVAS) support have increased because of prolonged wait times for transplant and the more frequent use of devices for destination therapy. The HeartMate LVAS, the only device approved for bridge to transplant and destination therapy, has limited durability, making replacement increasingly necessary. Since 1996, we have exchanged 19 left ventricular assist devices in 15 patients (11 men: mean age, 57.1 years; range, 33-77 years). Most of the devices (14) were replaced with the HeartMate vented electric/extended-lead vented electric pump; five devices were exchanged for a HeartMate II LVAS. Bearing failure was the most frequent reason for exchange (15 of 19 pumps); four of the 19 pumps also had active device-related infections at the time of exchange. There were no early deaths (30 days). Overall survival (Kaplan-Meier) was 85% at 1 year, 67% at 2 years, and 56% at 3 years. Three patients had transplants (mean, 518 days); six patients died during support (mean, 934 days), and six patients remain on LVAS support (mean, 1,219 days). One patient has been on device for over 6 years. Left ventricular assist devices exchange is becoming increasingly likely and can be associated with acceptably low-operative mortality rates and good intermediate-term survival.

Assessment of recurrent heart failure associated with left ventricular assist device dysfunction.

BACKGROUND: Patients with advanced heart failure may require long-term support with an intracorporeal left ventricular assist device (LVAD) before cardiac transplant, while awaiting myocardial recovery, or during destination therapy. Compared with the diagnosis of native heart dysfunction, there is less experience with the assessment of recurrent heart failure after LVAD placement. METHODS: Ten patients (9 men, 1 woman; age, 58 +/- 11 years) were studied after LVAD placement. Six patients were studied because of recurrent heart failure; the remaining 4 had other indications for study and are reported here as controls. Cardiac catheterization, including LVAD and cannulae catheterization, and angiography were performed. RESULTS: Inflow cannula valve regurgitation by LVAD angiography was found in 3 cases. Patients with regurgitation had a mean increased resting LVAD rate of 105 beats/min (range, 90-120); LVAD output exceeded forward cardiac output (LVAD - thermodilution cardiac output = +3.7 liters/min [0.6-6.4]). Inflow cannula obstruction identified with a filling phase pressure gradient between the left ventricle and the LVAD was found in 3 additional patients. Patients with obstruction had decreased resting LVAD rates (50 beats/min, all patients); LVAD output was less than the forward cardiac output (LVAD - thermodilution cardiac output = -2.3 liters/min [-0.8 to -3.5]). Compared with those with inflow valve regurgitation, patients with cannula obstruction had higher pulmonary capillary wedge pressures; phasic left ventricular pressure variation was reduced. Patients with cannula dysfunction underwent surgical intervention, and 4 of 6 were long-term survivors. CONCLUSIONS: When heart failure recurs after LVAD placement, abnormalities of the inflow cannula are common. Cardiac catheterization can confirm the diagnosis before surgical intervention. Hemodynamic coupling between the left ventricle and the LVAD is increased with inflow valve regurgitation and reduced with cannula obstruction.

Environmental influences on bovine kappa-casein: reduction and conversion to fibrillar (amyloid) structures.

The caseins of milk form a unique calcium-phosphate transport complex that provides these necessary nutrients to the neonate. The colloidal stability of these particles is primarily the result of kappa-casein. As purified from milk, this protein occurs as spherical particles with a weight average molecular weight of 1.18 million. The protein exhibits a unique disulfide bonding pattern, which (in the absence of reducing agents) ranges from monomer to octamers and above on SDS-PAGE. Severe heat treatment of the kappa-casein (90 degrees C) in the absence of SDS, before electrophoresis, caused an increase in the polymeric distribution: up to 40% randomly aggregated high-molecular weight polymers, presumably promoted by free sulfhydryl groups (J. Protein Chem. 17: 73-84, 1998). To ascertain the role of the sulfhydryl groups, the protein was reduced and carboxymethylated (RCM-K). Surprisingly, at only 37 degrees C, the RCM-kappa-casein exhibited an increase in weight average molecular weight and tendency to self-association when studied at 3000 rpm by analytical ultracentrifugation. Electron microscopy (EM) of the 37 degrees C RCM sample showed that, in addition to the spherical particles found in the native protein, there was a high proportion of fibrillar structures. The fibrillar structures were up to 600 nm in length. Circular dichroism (CD) spectroscopy was used to investigate the temperature-induced changes in the secondary structure of the native and RCM-kappa-caseins. These studies indicate that there was little change in the distribution of secondary structural elements during this transition, with extended strand and beta turns predominating. On the basis of three-dimensional molecular modeling predictions, there may exist a tyrosine-rich repeated sheet-turn-sheet motif in kappa-casein (residues 15-65), which may allow for the stacking of the molecules into fibrillar structures. Previous studies on amyloid proteins have suggested that such motifs promote fibril formation, and near-ultraviolet CD and thioflavin-T binding studies on RCM-kappa-casein support this concept. The results are discussed with respect to the role that such fibrils may play in the synthesis and secretion of casein micelles in lactating mammary gland.