Sorafenib in Hepatopulmonary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.

The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar-arterial oxygen gradient (AaPO2 ) at 3 months in patients with HPS. We performed a randomized, double-blind, placebo-controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, -3.8 to 7.0 mm Hg) and those allocated to placebo (-2.4 mm Hg; IQR, -4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2-expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.

Outcomes in the Randomized CoreValve US Pivotal High Risk Trial in Patients With a Society of Thoracic Surgeons Risk Score of 7% or Less.

Importance: Transcatheter aortic valve replacement (TAVR) is now a well-accepted alternative to surgical AVR (SAVR) for patients with symptomatic aortic stenosis at increased operative risk. There is interest in whether TAVR would benefit patients at lower risk. Objective: The Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) has trended downward in US TAVR trials and the STS/American College of Cardiology Transcatheter Valve Therapy Registry. We hypothesized that if the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) alone is sufficient to define decreased risk, the contribution to survival based on the degree of invasiveness of the TAVR procedure will decrease, making it more difficult to show improved survival and benefit over SAVR. Design, Setting, and Participants: The CoreValve US Pivotal High Risk Trial was a multicenter, randomized, noninferiority trial. This retrospective analysis evaluated patients who underwent an attempted implant and had an STS PROM of 7% or less. The trial was performed at 45 US sites. Patients had severe aortic stenosis and were at increased surgical risk based on their STS PROM score and other risk factors. Interventions: Eligible patients were randomly assigned (1:1) to self-expanding TAVR or to SAVR. Main Outcomes and Measures: We retrospectively stratified patients by the overall median STS PROM score (7%) and analyzed clinical outcomes and quality of life using the Kansas City Cardiomyopathy Questionnaire in patients with an STS PROM score of 7% or less. Results: The mean (SD) ages were 81.5 (7.6) years for the TAVR group and 81.2 years (6.6) for the SAVR group. A little more than half were men (57.9% in the TAVR group and 55.8% in the SAVR group). Of 750 patients who underwent attempted implantation, 383 (202 TAVR and 181 SAVR) had an STS PROM of 7% or less (median [interquartile range]: TAVR, 5.3% [4.3%-6.1%]; SAVR, 5.3% [4.1%-5.9%]). Two-year all-cause mortality for TAVR vs SAVR was 15.0% (95% CI, 8.9-10.0) vs 26.3% (95% CI, 19.7-33.0) (log rank P = .01). The 2-year rate of stroke for TAVR vs SAVR was 11.3% vs 15.1% (log rank P = .50). Quality of life by the Kansas City Cardiomyopathy Questionnaire summary score showed significant and equivalent increases in both groups at 2 years (mean [SD] TAVR, 20.0 [25.0]; SAVR, 18.6 [23.6]; P = .71; both P < .001 compared with baseline). Medical benefit, defined as alive with a Kansas City Cardiomyopathy Questionnaire summary score of at least 60 and a less than 10-point decrease from baseline, was similar between groups at 2 years (TAVR, 51.0%; SAVR, 44.4%; P = .28). Conclusions and Relevance: Self-expanding TAVR compares favorably with SAVR in high-risk patients with STS PROM scores traditionally considered intermediate risk. Trial Registration: Clinicaltrials.gov Identifier: NCT01240902.

Electrophysiological and hemodynamic characteristics associated with obesity in patients with atrial fibrillation.

OBJECTIVES: The authors sought to characterize the left atrial (LA) and pulmonary vein (PV) electrophysiological and hemodynamic features in obese patients with atrial fibrillation (AF). BACKGROUND: Obesity is associated with increased risk for AF. METHODS: A total of 63 consecutive patients with AF who had normal left ventricular (LV) ejection fraction and who underwent catheter ablation were studied. Atrial and PV electrophysiological studies were performed at the time of ablation with hemodynamic assessment by cardiac catheterization, and LA/LV structure and function by echocardiography. Patients were compared on the basis of body mass index (BMI): <25 kg/m(2) (n = 19) and BMI ≥30 kg/m(2) (n = 44). RESULTS: At a 600-ms pacing cycle length, obese patients had shorter effective refractory period (ERP) in the left atrium (251 ± 25 ms vs. 233 ± 32 ms, p = 0.04), and in the proximal (207 ± 33 ms vs. 248 ± 34 ms, p < 0.001) and distal (193 ± 33 ms vs. 248 ± 44 ms, p < 0.001) PV than normal BMI patients. Obese patients had higher mean LA pressure (15 ± 5 mm Hg vs. 10 ± 5 mm Hg, p < 0.001) and LA volume index (28 ± 12 ml/m(2) vs. 21 ± 14 ml/m(2), p = 0.006), and lower LA strain (5.5 ± 3.1% vs. 8.8 ± 2.8%; p < 0.001) than normal BMI patients. CONCLUSIONS: Increased LA pressure and volume, and shortened ERP in the left atrium and PV are potential factors facilitating and perpetuating AF in obese patients with AF.

The response of the vena cava to abdominal breathing.

BACKGROUND: Recently, abdominal-breathing or diaphragmatic-breathing methods have increased in popularity. Little is known how abdominal breathing affects the circulatory system. This study was designed to determine the impact of the respiratory pattern on central venous flow using echocardiography. METHODS: The superior vena cava (SVC) and inferior vena cava (IVC) were observed in people who had practiced abdominal breathing for at least 2 years, while they were breathing in three different techniques: slow respiration, slow respiration with inspiratory pause, or normal respiration. In addition, the observation during normal respiration was compared with that of a control group. RESULTS: The abdominal-breathing group consisted of 20 people with mean duration of training of 9.6 years. The respiratory collapsibility index of IVC during slow respiration with inspiratory pause was 62±19% compared with 48±19% during normal respiration (p=0.012) in the abdominal-breathing group. The abdominal-breathing group had a higher IVC collapsibility index compared to the control group during normal respiration (48±19% versus 26±12%, p<0.001), assuming a similar respiratory rate of about 10/min. Neither the size nor the minute flow of SVC differed among breathing patterns or between groups. CONCLUSIONS: The IVC of people who practice abdominal breathing has a greater degree of collapse than those of normal people, suggesting that abdominal-breathing exercise can positively affect venous return via IVC. For those who practice abdominal breathing, the collapsibility of the IVC is the best during slow respiration with inspiratory pause. The SVC did not seem to be affected by abdominal-breathing training.

The effect of chair massage on muscular discomfort in cardiac sonographers: a pilot study.

BACKGROUND: Cardiac sonographers frequently have work-related muscular discomfort. We aimed to assess the feasibility of having sonographers receive massages during working hours in an area adjacent to an echocardiography laboratory and to assess relief of discomfort with use of the massages with or without stretching exercises. METHODS: A group of 45 full-time sonographers was randomly assigned to receive weekly 30-minute massage sessions, massages plus stretching exercises to be performed twice a day, or no intervention. Outcome measures were scores of the QuickDASH instrument and its associated work module at baseline and at 10 weeks of intervention. Data were analyzed with standard descriptive statistics and the separation test for early-phase comparative trials. RESULTS: Forty-four participants completed the study: 15 in the control group, 14 in the massage group, and 15 in the massage plus stretches group. Some improvement was seen in work-related discomfort by the QuickDASH scores and work module scores in the 2 intervention groups. The separation test showed separation in favor of the 2 interventions. CONCLUSION: On the basis of the results of this pilot study, larger trials are warranted to evaluate the effect of massages with or without stretching on work-related discomfort in cardiac sonographers. TRIAL REGISTRATION: NCT00975026 ClinicalTrials.gov.

Safety, acceptance, and physiologic effects of sauna bathing in people with chronic heart failure: a pilot report.

OBJECTIVES: To perform a pilot study and make a preliminary assessment of the safety and acceptance of supervised sauna bathing at moderate temperatures in people with chronic heart failure (CHF). Secondary measures included its impact on exercise tolerance and neuroendocrine concentrations. DESIGN: Randomized, controlled, cross-over trial. SETTING: Physical medicine and rehabilitation clinic. PARTICIPANTS: Six men and 3 women (age, 62-87y) with New York Heart Association Class III and IV CHF. INTERVENTIONS: Subjects were randomized into 2 groups and told to maintain their normal medication and activity regimens. One group then began a 3-times-a-week, 4-week sauna bathing program at 60+/-1 degrees C while the other continued with their usual activities and medications. Assignments were then reversed. Sessions were 15 minutes in length but were prolonged an additional 5 minutes for oral temperature increases less than 1.0 degrees C. MAIN OUTCOME MEASURES: Patient acceptance, Minnesota Living With Heart Failure Questionnaire (MLWHFQ) scores; treadmill exercise duration and plasma adrenaline, noradrenalin, aldosterone, atrial naturectic factor, adrenomedulin, and endothelin. RESULTS: Sauna bathing was well tolerated and no adverse effects were reported. Improvements in MLWHFQ scores and treadmill endurance did not achieve statistical significance on a between-group basis but were more marked after the sauna than during the control phase. Neuroendocrine concentrations showed no clear effect of sauna treatment with a between-group statistically significant difference (P=.049) found only in the case of noradrenalin's 24% decrease. CONCLUSIONS: Sauna bathing under the moderate and supervised conditions of this study appears to be well tolerated and may be safe for people with CHF. More research is needed to further evaluate the safety and potential benefits of this approach.

Acute Myocardial Infarction with Hyperoxemic Therapy (AMIHOT): a prospective, randomized trial of intracoronary hyperoxemic reperfusion after percutaneous coronary intervention.

OBJECTIVES: This study sought to determine whether hyperoxemic reperfusion with aqueous oxygen (AO) improves recovery of ventricular function after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: Hyperbaric oxygen reduces myocardial injury and improves ventricular function when administered during ischemia-reperfusion. METHODS: In a prospective, multicenter study, 269 patients with acute anterior or large inferior AMI undergoing primary or rescue PCI (<24 h from symptom onset) were randomly assigned after successful PCI to receive hyperoxemic reperfusion (treatment group) or normoxemic blood autoreperfusion (control group). Hyperoxemic reperfusion was performed for 90 min using intracoronary AO. The primary end points were final infarct size at 14 days, ST-segment resolution, and delta regional wall motion score index of the infarct zone at 3 months. RESULTS: At 30 days, the incidence of major adverse cardiac events was similar between the control and AO groups (5.2% vs. 6.7%, p = 0.62). There was no significant difference in the incidence of the primary end points between the study groups. In post-hoc analysis, anterior AMI patients reperfused <6 h who were treated with AO had a greater improvement in regional wall motion (delta wall motion score index = 0.54 in control group vs. 0.75 in AO group, p = 0.03), smaller infarct size (23% of left ventricle in control group vs. 9% of left ventricle in AO group, p = 0.04), and improved ST-segment resolution compared with normoxemic controls. CONCLUSIONS: Intracoronary hyperoxemic reperfusion was safe and well tolerated after PCI for AMI, but did not improve regional wall motion, ST-segment resolution, or final infarct size. A possible treatment effect was observed in anterior AMI patients reperfused <6 h of symptom onset.

Intracardiac phased-array imaging: methods and initial clinical experience with high resolution, under blood visualization: initial experience with intracardiac phased-array ultrasound.

OBJECTIVES: This study was designed to test the feasibility of high-resolution phased-array intracardiac imaging. BACKGROUND: Intracardiac echocardiographic imaging of the heart during interventional electrophysiologic (EP) procedures has been limited by inadequate ultrasound penetration and absence of Doppler hemodynamic and flow information produced by rotating mechanical ultrasound elements. METHODS: A 10F (3.2 mm) phased-array, variable 5.5 to 10 MHz frequency imaging catheter with a four-way deflectable tip was applied in 24 patients undergoing EP studies. Sixteen prespecified cardiac targets were imaged from a right heart venue. RESULTS: Fifteen patients had no underlying organic heart disease; nine had ischemic, cardiomyopathic, valvular or congenital heart disorders. Longitudinal and short-axis imaging readily disclosed each cardiac valve, support structures and chamber, as well as the pericardium, right and left atrial appendages, the junction of the right atrium and superior vena cava, crista terminalis, tricuspid valve isthmus, coronary sinus orifice, membranous fossa ovalis and pulmonary veins. The average target depth was 8.8+/-1.5 cm (range 0.5 to 15 cm), with adequate penetration at a 7.5 MHz imaging frequency. Color flow and Doppler utilities clearly characterized transaortic and pulmonic valve and pulmonary vein blood flow, including during low output states. CONCLUSIONS: These first human studies with this technology demonstrate the methods, feasibility and utility of intracardiac phased-array vector and Doppler imaging for long-axis, apex-to-base global cardiac imaging. High resolution of endocardial structures and catheters suggests additional utility for visualizing interventional procedures from the right heart.