The Effects of the ManageHF4Life Mobile App on Patients With Chronic Heart Failure: Randomized Controlled Trial.

BACKGROUND: The successful management of heart failure (HF) involves guideline-based medical therapy as well as self-management behavior. As a result, the management of HF is moving toward a proactive real-time technological model of assisting patients with monitoring and self-management. OBJECTIVE: The aim of this paper was to evaluate the efficacy of enhanced self-management via a mobile app intervention on health-related quality of life, self-management, and HF readmissions. METHODS: A single-center randomized controlled trial was performed. Participants older than 45 years and admitted for acute decompensated HF or recently discharged in the past 4 weeks were included. The intervention group ("app group") used a mobile app, and the intervention prompted daily self-monitoring and promoted self-management. The control group ("no-app group") received usual care. The primary outcome was the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 6 and 12 weeks. Secondary outcomes were the Self-Care Heart Failure Index (SCHFI) questionnaire score and recurrent HF admissions. RESULTS: A total of 83 participants were enrolled and completed all baseline assessments. Baseline characteristics were similar between the groups except for the prevalence of ischemic HF. The app group had a reduced MLHFQ at 6 weeks (mean 37.5, SD 3.5 vs mean 48.2, SD 3.7; P=.04) but not at 12 weeks (mean 44.2, SD 4 vs mean 45.9, SD 4; P=.78), compared to the no-app group. There was no effect of the app on the SCHFI at 6 or 12 weeks. The time to first HF readmission was not statistically different between the app group and the no-app group (app group 11/42, 26% vs no-app group 12/41, 29%; hazard ratio 0.89, 95% CI 0.39-2.02; P=.78) over 12 weeks. CONCLUSIONS: The adaptive mobile app intervention, which focused on promoting self-monitoring and self-management, improved the MLHFQ at 6 weeks but did not sustain its effects at 12 weeks. No effect was seen on HF self-management measured by self-report. Further research is needed to enhance engagement in the app for a longer period and to determine if the app can reduce HF readmissions in a larger study. TRIAL REGISTRATION: ClinicalTrials.gov NCT03149510; https://clinicaltrials.gov/ct2/show/NCT03149510.

Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART).

BACKGROUND: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis. METHODS: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis. DISCUSSION: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

Aortic Valve Repair Versus Replacement Associated With Durable Left Ventricular Assist Devices.

BACKGROUND: Aortic valve (AV) repair (AVr) using a central coaptation stitch or bioprosthetic AV replacement (AVR) are most commonly performed at the time of durable left ventricular assist device implant to address AV insufficiency (AI). METHODS: Prospective data collection on 46 patients undergoing left ventricular assist device implant from 2007 through 2018 who received concomitant AVr (n = 40) or AVR (n = 6) was retrospectively analyzed to assess freedom from recurrent aortic insufficiency. Paired Wilcoxon rank-sum test was used to compare echocardiographic findings. Mantel-Cox statistics were used to analyze survival. RESULTS: For AVr, central coaptation led to a mean decrease in AI severity by 2.1 ± 1.0 grades (P < .001). Three patients (7.5%) had recurrence of at least moderate AI by 3 years. In comparison, all patients in the AVR group had mild or less AI on subsequent follow-up. Success of AVr in downgrading AI severity was associated with a smaller aortic root diameter (P = .011) and sinotubular junction diameter (P = .003). An aortic root diameter greater than 3.5 cm was predictive of less improvement in AI severity compared with 3.5 cm or less (1.83 ± 1.03 versus 2.47 ± 0.80 grades of improvement; P = .038). Duration of cardiopulmonary bypass was 32 minutes longer and duration of aortic cross-clamp was 38 minutes longer for AVR versus AVr cohorts. No difference in 30-day (P = .418) or overall survival (P = .572) between the AVr and AVR groups was seen. CONCLUSIONS: Aortic valve repair for addressing AI has a recurrence rate of 7.5% at 3 years. Success in downgrading AI is more likely with a smaller aortic root. No difference in survival was observed between AVr and AVR.

Safety of regadenoson positron emission tomography stress testing in orthotopic heart transplant patients.

OBJECTIVES: We sought to determine the safety of regadenoson (REG) stress testing in patients who have undergone orthotopic heart transplantation (OHT). BACKGROUND: Routine screening for cardiac allograft vasculopathy (CAV) is necessary after OHT. Adenosine stress is contraindicated after heart transplantation due to supersensitivity in denervated hearts. Safety of regadenoson stress following OHT has not been well studied. METHODS: We retrospectively reviewed data from OHT patients (N = 123) who were referred to REG stress testing. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson and to identify adverse reactions. RESULTS: No serious adverse events occurred. No life-threatening arrhythmias or hemodynamic changes occurred. Common side-effects related to regadenoson were observed, dyspnea being the most frequent (66.7%). On average the heart rate rose from 82.8 ± 12 to 95.7 ± 13.4 bpm (P < 0.001), systolic blood pressure decreased from 138.7 ± 20.9 to 115.9 ± 23.9 mmHg (P < 0.001) and mean arterial pressure decreased from 103.5 ± 14.1 to 84.72 ± 15.90 mmHg (P < 0.001) during stress protocol. There was no sustained ventricular tachycardia, ventricular fibrillation, or second-or third-degree atrioventricular block. CONCLUSION: Regadenoson stress testing appears to be well tolerated and safe in OHT patients.

Ischemic Cardiac Events Following Treatment of the Internal Mammary Nodal Region Using Contemporary Radiation Planning Techniques.

PURPOSE: Regional nodal irradiation, including radiation therapy (RT) to the internal mammary node (IMN) region, improves oncologic outcomes in patients with node-positive breast cancer. Concern remains, however, given the proximity of the IMNs to the heart and the association between cardiac RT exposure and toxicity. The objective of the study was to evaluate rates of ischemic cardiac events (ICEs) and associated risk with treatment of the IMN region. METHODS AND MATERIALS: The cardiac outcomes of 2126 patients treated with adjuvant breast RT or breast and nodal RT from 1984 to 2007 at a single institution were reviewed. The primary endpoint was an ICE following RT initiation. The association between IMN RT and ICEs was assessed using Cox proportional hazards models. Treatment with both IMN RT and 3-dimensional (3D) conformal radiation therapy (CRT) began in 1997; therefore, subset analyses of patients with only 3D CRT were performed to minimize bias associated with improved treatment technique. RESULTS: The median follow-up period was 9.3 years. An ICE occurred in 87 patients (4.1%). No increased 10-year rate of ICEs was observed with IMN RT compared with no IMN RT in the total cohort (3.2% [95% confidence interval (CI), 2.4%-4.3%] vs 3.4% [95% CI, 1.5%-7.5%]; hazard ratio [HR], 0.88; P=.73). Similarly, no statistically significant difference was noted in the 3D CRT-planned, left-sided disease subset (5.1% [95% CI, 1.8%-14.1%] vs 4.0% [95% CI, 2.0%-8.0%]; HR, 1.18, P=.76). On multivariate analysis, adjusting for cardiac risk factor imbalances, no significantly increased hazard was noted with IMN RT (HR, 1.84; P=.28) in the 3D CRT-planned, left-sided disease subset. CONCLUSIONS: No statistically significant association between IMN RT and ICEs was demonstrated in a review of patients treated at a single institution from 1984 to 2007. Given the long natural history and low overall rate of ICEs, continued follow-up of this study, as well as additional studies in the 3D CRT era, is warranted to confirm these results. Minimizing cardiac exposure, when treating a limited IMN field, is critical to limit excess risk of ICEs.

Effects of Total Dose Infusion of Iron Intravenously in Patients With Acute Heart Failure and Anemia (Hemoglobin < 13 g/dl).

Iron deficiency is common in heart failure (HF), and intravenous (IV) iron therapy has been associated with improved clinical status in ambulatory patients with HF. There are limited data to support the safety and efficacy of IV iron administration in patients with acute HF. This was a retrospective cohort study of patients admitted to the University of Michigan Health System for HF with low iron studies during admission. Patients were grouped based on the receipt of IV iron therapy. Study outcomes included change in hemoglobin, 30-day readmission, and adverse events. Forty-four patients who received IV iron and 128 control patients were identified. The mean dose of IV iron received was 1,057 (±336) mg. IV iron resulted in a significantly greater increase in hemoglobin over time (p = 0.0001). The mean change in hemoglobin in the iron and control groups was 0.74 g/dl and 0.01 g/dl at day 7 and 2.61 g/dl and 0.23 g/dl at day 28, respectively. Thirty-day readmission rates were 30% and 22% for patients in the iron and control groups, respectively (p = 0.2787). In conclusion, total dose infusion IV iron is well tolerated and associated with significant improvement in hemoglobin in acute HF.

Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients.

BACKGROUND: Hospitalized advanced heart failure (HF) patients are at high risk for malnutrition and death. The Nutritional Risk Index (NRI) is a simple, well-validated tool for identifying patients at risk for nutrition-related complications. We hypothesized that, in advanced HF patients from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial, the NRI would improve risk discrimination for 6-month all-cause mortality. METHODS: We analyzed the 160 ESCAPE index admission survivors with complete follow-up and NRI data, calculated as follows: NRI = (1.519 × discharge serum albumin [in g/dl]) + (41.7 × discharge weight [in kg] / ideal body weight [in kg]); as in previous studies, if discharge weight is greater than ideal body weight (IBW), this ratio was set to 1. The previously developed ESCAPE mortality model includes: age; 6-minute walk distance; cardiopulmonary resuscitation/mechanical ventilation; discharge ß-blocker prescription and diuretic dose; and discharge serum sodium, blood urea nitrogen and brain natriuretic peptide levels. We used Cox proportional hazards modeling for the outcome of 6-month all-cause mortality. RESULTS: Thirty of 160 patients died within 6 months of hospital discharge. The median NRI was 96 (IQR 91 to 102), reflecting mild-to-moderate nutritional risk. The NRI independently predicted 6-month mortality, with adjusted HR 0.60 (95% CI 0.39 to 0.93, p = 0.02) per 10 units, and increased Harrell's c-index from 0.74 to 0.76 when added to the ESCAPE model. Body mass index and NRI at hospital admission did not predict 6-month mortality. The discharge NRI was most helpful in patients with high (≥ 20%) predicted mortality by the ESCAPE model, where observed 6-month mortality was 38% in patients with NRI < 100 and 14% in those with NRI > 100 (p = 0.04). CONCLUSIONS: The NRI is a simple tool that can improve mortality risk stratification at hospital discharge in hospitalized patients with advanced HF.

Changes in serial B-type natriuretic peptide level independently predict cardiac allograft rejection.

BACKGROUND: Despite positive associations with rejection, the clinical value of B-type natriuretic peptide (BNP) monitoring in heart transplant recipients has not been established. We sought to determine the predictive value of changes in serial BNP level for identifying patients with acute allograft rejection. METHODS: BNP, hemodynamics and biopsies were obtained for 205 transplant recipients who underwent a total of 4,007 endomyocardial biopsy procedures. Samples analyzed were collected ≥ 180 days post-transplant, without evidence of rejection on the immediately preceding biopsy. Using a repeated-measures multivariate model, we assessed the association of change in BNP with Grade ≥ 3A (2R) rejection. We also determined predictive values of various cut-off thresholds of change in serial BNP levels to predict Grade ≥ 3A rejection. RESULTS: There were 47 episodes of Grade ≥ 3A rejection among the 1,350 samples analyzed. Median change in serial BNP (ΔBNP) for those with Grade ≥ 3A rejection was 20 pg/ml (IQR -26 to 169 pg/ml) and among those with Grade <3A rejection was -4 pg/ml (IQR -34 to 22 pg/ml, p = 0.003). On multivariate analysis, ΔBNP remained the most potent independent predictor of Grade ≥ 3A rejection (p = 0.001). ΔBNP >100 pg/ml predicted increased risk of Grade ≥ 3A rejection (OR = 5.3, p < 0.001) with high specificity (93.3%) and positive predictive value (13.0%) and excellent negative predictive value (97.3%). CONCLUSIONS: Change in serial BNP level is an independent predictor of cardiac allograft rejection. With wide availability, rapid turnaround, low cost, favorable positive predictive value and excellent negative predictive value, serial BNP monitoring has several advantages for non-invasive monitoring of heart transplant recipients for acute cardiac allograft rejection.

Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer.

PURPOSE: Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. METHODS AND MATERIALS: A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. RESULTS: The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. CONCLUSIONS: This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.

Model for end-stage liver disease score predicts left ventricular assist device operative transfusion requirements, morbidity, and mortality.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) predicts events in cirrhotic subjects undergoing major surgery and may offer similar prognostication in left ventricular assist device candidates with comparable degrees of multisystem dysfunction. METHODS AND RESULTS: Preoperative MELD scores were calculated for subjects enrolled in the University of Michigan Health System (UMHS) mechanical circulatory support database. Univariate and multiple regression analyses were performed to investigate the ability of patient characteristics, laboratory data (including MELD scores), and hemodynamic measurements to predict total perioperative blood product exposure and operative mortality. The ability of preoperative MELD scores to predict operative mortality was evaluated in subjects enrolled in the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), and results were compared with those from the UMHS cohort. The mean+/-SD MELD scores for the UMHS (n=211) and INTERMACS (n=324) cohorts were 13.7+/-6.1 and 15.2+/-5.8, respectively, with 29 (14%) and 19 (6%) perioperative deaths. In the UMHS cohort, median total perioperative blood product exposure was 74 units (25th and 75th percentiles, 44 and 120 units). Each 5-unit MELD score increase was associated with 15.1+/-3.8 units (beta+/-SE) of total perioperative blood product exposure. Each 10-unit increase in total perioperative blood product exposure increased the odds of operative death (odds ratio, 1.05; 95% confidence interval, 1.01 to 1.10). Odds ratios, measuring the ability of MELD scores to predict perioperative mortality, were 1.5 (95% confidence interval, 1.1 to 2.0) and 1.5 (95% confidence interval, 1.1 to 2.1) per 5 MELD units for the UMHS and INTERMACS cohorts, respectively. When MELD scores were dichotomized as >or=17 and <17, risk-adjusted Cox proportional-hazard ratios for 6-month mortality were 2.5 (95% confidence interval, 1.2 to 5.3) and 2.5 (95% confidence interval, 1.1 to 5.4) for the UMHS and INTERMACS cohorts, respectively. CONCLUSIONS: The MELD score identified left ventricular assist device candidates at high risk for perioperative bleeding and mortality.

The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates.

OBJECTIVES: This study sought to develop a model that estimates the post-operative risk of right ventricular (RV) failure in left ventricular assist device (LVAD) candidates. BACKGROUND: Right ventricular failure after LVAD surgery is associated with increased morbidity and mortality, but identifying LVAD candidates at risk for RV failure remains difficult. METHODS: A prospectively collected LVAD database was evaluated for pre-operative clinical, laboratory, echocardiographic, and hemodynamic predictors of RV failure. Right ventricular failure was defined as the need for post-operative intravenous inotrope support for >14 days, inhaled nitric oxide for > or =48 h, right-sided circulatory support, or hospital discharge on an inotrope. An RV failure risk score (RVFRS) was created from multivariable logistic regression model coefficients, and a receiver-operating characteristic curve of the score was generated. RESULTS: Of 197 LVADs implanted, 68 (35%) were complicated by post-operative RV failure. A vasopressor requirement (4 points), aspartate aminotransferase > or =80 IU/l (2 points), bilirubin > or =2.0 mg/dl (2.5 points), and creatinine > or =2.3 mg/dl (3 points) were independent predictors of RV failure. The odds ratio for RV failure for patients with an RVFRS < or =3.0, 4.0 to 5.0, and > or =5.5 were 0.49 (95% confidence interval [CI] 0.37 to 0.64), 2.8 (95% CI 1.4 to 5.9), and 7.6 (95% CI 3.4 to 17.1), respectively, and 180-day survivals were 90 +/- 3%, 80 +/- 8%, and 66 +/- 9%, respectively (log rank for linear trend p = 0.0045). The area under the receiver-operating characteristic curve for the RVFRS (0.73 +/- 0.04) was superior to that of other commonly used predictors of RV failure (all p < 0.05). CONCLUSIONS: The RVFRS, composed of routinely collected, noninvasive pre-operative clinical data, effectively stratifies the risk of RV failure and death after LVAD implantation.

Rates of myocardial infarction and coronary artery disease and risk factors in patients treated with radiation therapy for early-stage breast cancer.

BACKGROUND: Radiation therapy (RT), a critical component of breast-conserving therapy for breast cancer, has been associated with coronary artery disease (CAD) in numerous older studies, but the risk may be lower with modern techniques. METHODS: Observed rates of cardiac events in 828 patients treated with breast-conserving surgery and RT at the University of Michigan were compared with expected rates. Relations between potential risk factors and actuarial rates of first CAD event were analyzed. RESULTS: Observed risks of cardiac events were lower than expected. The standardized incidence ratio (SIR) of myocardial infarction (MI) was 0.44 (95% confidence interval [CI]: 0.21-0.70). The SIR of MI or CAD requiring intervention was 0.50 (95% CI: 0.27-0.68). With a median follow-up of 6.8 years, 12 (1.4%) patients had at least 1 MI on follow-up and 20 (2.4%) had at least 1 MI or CAD requiring intervention. Median age at first cardiac event was 75.9 years (range, 43.1-91.5). Median interval from RT to occurrence of the first cardiac event was 3.7 years (range, 13 days to 15.4 years). The 10-year cumulative incidence of MI was 1.2% and cumulative incidence of MI or CAD requiring intervention was 2.7%. On multivariate analysis, age, diabetes mellitus, active smoking, and laterality of RT were significant predictors of MI. Age and active smoking were significant predictors of MI or CAD requiring intervention. CONCLUSIONS: Patients in this series had lower risk of ischemic cardiac events than expected. Although small in absolute magnitude, patients radiated to the left side did have a statistically significant increased risk of MI. These findings support further investigation of techniques to minimize the long-term cardiac risks faced by breast cancer patients.

Stroke rates and risk factors in patients treated with radiation therapy for early-stage breast cancer.

PURPOSE: To examine whether stroke risk is elevated in American breast cancer patients treated with modern techniques, as well as whether supraclavicular radiation therapy (RT) is associated with increased risk. METHODS: Observed rates of stroke in 820 eligible early-stage breast cancer patients treated at the University of Michigan Hospital (Ann Arbor, MI) were compared with expected rates. Relationships between potential risk factors and actuarial rate of first stroke were analyzed. RESULTS: Median follow-up was 6.8 years. Twenty patients had at least one cerebrovascular accident (CVA) in follow-up; 35 patients had at least one CVA or transient ischemic attack (CVA/TIA). The standardized incidence ratios were 1.74 (0.94 to 2.37) for CVA and 1.68 (1.003 to 2.06) for CVA/TIA. The absolute excess risk per 1,000 patients per year was 1.67 for CVA and 2.76 for CVA/TIA. On bivariate analysis, factors significantly associated with actuarial rate of first CVA included hypertension (P = .002), age (P < .0001), coronary artery disease (P = .001), atrial fibrillation (P = .009), and supraclavicular RT (P = .021). Factors associated with CVA/TIA were hypertension (P < .001), coronary artery disease (P = .002), and age (P < .0001). Tamoxifen use alone was not significant (P = .19), but tamoxifen combined with baseline hypertension led to increased risk of CVA/TIA (log-rank P < .0001). On multivariate analysis, only age (P < .001) and hypertension (P = .003) remained significant predictors of CVA/TIA. Age was the only significant predictor of CVA alone (P < .001). CONCLUSION: American breast cancer survivors may have an elevated risk of stroke compared with the general population, but the absolute excess risk is low. This study found no significant association between supraclavicular RT and stroke after controlling for other factors.

Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess effects of mitral valve annuloplasty (MVA) on mortality in patients with mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction. BACKGROUND: Mitral valve annuloplasty improves hemodynamics and symptoms in these patients, but effects on long-term mortality are not well established. METHODS: We retrospectively analyzed consecutive patients with significant MR and LV systolic dysfunction on echocardiography between 1995 and 2002. Cox regression analysis, including MVA as a time-dependent covariate and propensity scoring to adjust for differing probabilities of undergoing MVA, was used to identify predictors of death, LV assist device implantation, or United Network for Organ Sharing-1 heart transplantation. RESULTS: Of 682 patients identified, 419 were deemed surgical candidates; 126 underwent MVA. Propensity score derivation identified age, ejection fraction, and LV dimension to be associated with undergoing MVA. End points were reached in 120 (41%) non-MVA and 62 (49%) MVA patients. Increased risk of end point was associated with coronary artery disease (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.30 to 2.49), blood urea nitrogen (HR 1.01, 95% CI 1.005 to 1.02), cancer (HR 2.77, 95% CI 1.45 to 5.30), and digoxin (HR 1.66, 95% CI 1.15 to 2.39). Reduced risk was associated with angiotensin-converting enzyme inhibitors (HR 0.65, 95% CI 0.44 to 0.95), beta-blockers (HR 0.59, 95% CI 0.42 to 0.83), mean arterial pressure (HR 0.98, 95% CI 0.97 to 0.99), and serum sodium (HR 0.93, 95% CI 0.90 to 0.96). Mitral valve annuloplasty did not predict clinical outcome. CONCLUSIONS: In this analysis, there is no clearly demonstrable mortality benefit conferred by MVA for significant MR with severe LV dysfunction. A prospective randomized control trial is warranted for further study of mortality with MVA in this population.

Brain natriuretic peptide predicts serious cardiac allograft rejection independent of hemodynamic measurements.

BACKGROUND: Serum brain natriuretic peptide (BNP) has been reported to be elevated in heart transplant recipients with both cellular and vascular rejection. Whether BNP can be used to help predict the severity of rejection is not well established. METHODS: We analyzed serial BNP measurements obtained during endomyocardial biopsy procedures in consecutive heart transplant patients occurring >45 days after transplantation. To eliminate potential confounding from prior rejection episodes, we included only observations in which the previous biopsy grade was 0 or 1A. Multivariable linear regression was performed examining the outcome of increasing seriousness of rejection, defined as grade 0 < 1A < 2 < 1B < 3A < vascular rejection. A univariable logistic regression model was performed using log-transformed BNP as a predictor of vascular rejection. RESULTS: There were 77 patients, with 161 separate observations. Median time between transplantation and first assessment was 6.0 months (interquartile range, 2.1, 31.6). Using multivariable linear regression, 3 factors were significantly associated with biopsy score: pulmonary capillary wedge pressure (p < 0.0001), BNP (p = 0.003), and heart rate (p = 0.01). Even after other significant univariable predictors (including pulmonary capillary wedge pressure) were forced into the model, BNP remained a significant predictor of biopsy score (p = 0.02). Log BNP was a significant univariable predictor of vascular rejection, with an odds ratio of 12.55 (per 1 unit increase, 95% confidence interval 3.43-45.84; p = 0.0001) and a model c-statistic of 0.91. CONCLUSIONS: BNP predicts new episodes of serious cardiac allograft rejection, particularly vascular rejection, independent of hemodynamic measurements, and may be a useful part of rejection surveillance.

Cardiac chamber and coronary artery doses associated with postmastectomy radiotherapy techniques to the chest wall and regional nodes.

PURPOSE: To compare the estimated radiation doses delivered to the cardiac chambers (CC) and coronary arteries (CA) for 5 postmastectomy radiotherapy (PMRT) techniques. METHODS AND MATERIALS: A dosimetry study of 20 left-sided PMRT cases was conducted. Cardiac chambers (left and right atria [LA/RA] and left and right ventricles [LV/RV]) and coronary vessels (left main [LM], left anterior descending [LAD], left circumflex [LCX], right coronary [RCA] and posterior descending [PDA] arteries) were contoured on contrast-enhanced CT scans and verified by a cardiologist (T.K.). Five PMRT techniques were applied to each case; 50 Gy in 2 Gy fractions was delivered to the chest wall +/- internal mammary node targets. The techniques were: (1) standard tangents (TAN); (2) cobalt (Co); (3) reverse hockey stick (RHS); (4) mixed photon/electron beam (20/80); and (5) partially wide tangent fields (PWTF). Three-dimensional dose calculations for 100 plans were performed for all structures. Plans were compared by using the mean dose (Dmean) and the volume that received more than 30 Gy (V(30)) and 45 Gy (V(45)) for each structure. RESULTS: Cobalt and 20/80 techniques delivered higher Dmeans to the whole heart and individual cardiac chambers (RA, RV, LA, and LV) as compared with the other three techniques. The heart received a Dmean of 21.03 +/- 3.5 Gy from Co and 11.87 +/- 5.22 Gy from 20/80. The remaining techniques delivered heart Dmeans of 2.90-4.94 Gy. When V(30) was used as a metric, all techniques had comparably low V(30) to the heart, except for Co, which resulted in a significantly higher irradiated volume of right-sided cardiac chambers (59.06% +/- 30.7 for RA F-test < 0.0001; and 61.46% +/- 22.13 for RV, F-test < 0.0001). Dmean to the proximal LAD (LAD_p) was significantly higher for RHS (17.64 +/- 7.43 Gy) and 20/80 (20.52 +/- 8.36 Gy) and lowest for PWTF (9.5 +/- 4.16 Gy). The Dmean for the distal LAD (LAD_d) was significantly lower with PWTF (11.02 +/- 7.34 Gy) than with all other techniques, including TAN (p < 0.0001). Similar results for PWTF and TAN were observed when V30 and V45 were used. CONCLUSIONS: Cardiac substructures receive the most radiation exposure after PMRT with CO, 20/80 or both and least exposure with PWTF. Although TAN resulted in significant sparing of the majority of the cardiac structures, a significantly higher dose and volume of LAD was exposed when compared with PWTF. Although the clinical relevance of these dose differences is not clearly understood, these dosimetric estimates can serve as a baseline in the development of new techniques for locoregional treatment that will further reduce cardiac exposure.

Left ventricular diastolic function in patients with advanced cystic fibrosis.

OBJECTIVES: To assess left ventricular systolic and diastolic function in adult patients with cystic fibrosis using radionuclide ventriculography. BACKGROUND: Although myocardial fibrosis has been described in autopsy specimens of patients with cystic fibrosis, the possibility that myocardial dysfunction may occur during life in adult patients with cystic fibrosis has not been explored. METHODS: To assess the possibility of cardiac dysfunction occurring in cystic fibrosis, we studied 40 patients with advanced cystic fibrosis with first-pass radionuclide ventriculography and compared them to 9 patients with advanced bronchiectasis and 18 normal control subjects. RESULTS: Indexes of right ventricular systolic function were similarly impaired in patients with cystic fibrosis and patients with bronchiectasis. Left ventricular ejection fraction of patients with cystic fibrosis, patients with bronchiectasis, and normal control subjects did not differ. Fractional left ventricular filling at 50% of diastole, an index of diastolic function, was significantly lower in patients with cystic fibrosis (54 +/- 13%, mean +/- SD) in comparison to patients with bronchiectasis (66 +/- 4%, p = 0.009) or normal control subjects (69 +/- 14, p = 0.0002). The contribution of atrial systole to total diastolic left ventricular filling was greater in patients with cystic fibrosis (38 +/- 18%) than in patients with bronchiectasis (21 +/- 4%, p = 0.01) or normal control subjects (25 +/- 12%, p = 0.01). CONCLUSIONS: Patients with advanced cystic fibrosis demonstrate impaired left ventricular distensibility when compared to normal control subjects and patients with bronchiectasis. Patients with cystic fibrosis may be at risk of heart failure due to right ventricular dysfunction or left ventricular diastolic dysfunction.

Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) frequently develop in patients with left ventricular systolic dysfunction (LVSD). Ventricular volume overload that occurs in patients with MR and TR may lead to progression of myocardial dysfunction. We hypothesized that MR and TR would provide markers of risk in patients with LVSD. METHODS: We reviewed clinical, electrocardiographic, and echocardiographic data on 1421 consecutive patients with LVSD (left ventricular ejection fraction < or =35%). Predictors of survival (freedom from death or United Network for Organ Sharing [UNOS]-1 transplantation) were identified in a multivariable analysis with a Cox proportional hazards analysis. The impact of MR and TR (none to mild, moderate, or severe) then was assessed separately with Kaplan-Meier survival analysis. RESULTS: During the follow-up period (mean +/- SD, 365 +/-364 days), death occurred in 435 study subjects (31%) and UNOS-1 transplantation in 28 subjects (2%). Multivariable predictors of poor outcome included increasing MR and TR grade, cancer, coronary artery disease, and absence of an implantable cardiac defibrillator. Relative risk was 1.84 (95% CI 1.43-2.38) for severe MR and 1.55 (95% CI 1.14-2.11) for severe TR. Survival with Kaplan-Meier analysis related inversely to MR grade (none to mild 1004 +/-31 days, moderate 795 +/-34 days, severe 628 +/-47 days, P <.0001) and TR grade (none to mild 977 +/-28 days, moderate 737 +/-40 days, severe 658 +/-55 days, P =.0001). CONCLUSION: Patients with severe MR or TR represent high-risk subsets of patients with LVSD. Future study is warranted to determine whether pharmaceutical or surgical strategies to relieve MR and TR have a favorable impact on survival.

Outcome following mitral valve replacement in patients with mitral stenosis and moderately reduced left ventricular ejection fraction.

BACKGROUND: Some patients with mitral stenosis (MS) have moderately reduced left ventricular (LV) ejection fraction (EF), due to either depressed myocardial contractility or alterations in loading conditions. The effect of moderately reduced LV EF on outcome after mitral valve replacement (MVR) is not known. METHODS: We studied 16 consecutive patients with LV EF < or = 0.50 and MS without significant mitral regurgitation or other valvular or coronary artery disease (Group I). We selected four controls with LV EF >0.50 for each patient, matched for time of surgery (Group II, n=64). Mean EF in Groups I and II was 0.45 and 0.66, respectively. We compared short- and long-term outcome between the two groups. RESULTS: There were no perioperative deaths. Group I patients had a higher incidence of in-hospital postoperative heart failure (25% vs. 6%, P=0.02). Mean follow-up was 9 years in both groups. Mean New York Heart Association class improved from 2.4 to 1.7 in both groups. Group I patients had a higher incidence of heart failure deaths (13% vs. 2%, P=0.03) and admissions (40% vs. 13%, P=0.01). There were, however, no differences between Groups I and II in overall mortality (27% vs. 21%), rate of cardiac admissions (69% vs. 53%), or mean Specific Activity Scale Score (2.5 vs. 2.5). CONCLUSIONS: Although patients with MS and moderately reduced LV EF are at higher risk for heart failure after MVR, overall mortality is not different from that of patients with normal EF. Moderate depression of LV EF should not be a contraindication to MVR for MS.