Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension.

AIMS: A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and haemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH-LHD) and chronic lung disease (PH-CLD). METHODS AND RESULTS: Eight patients with PH-LHD and 10 patients with PH-CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas-filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Haemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. No complications or investigational device-related serious adverse events occurred. Device activation in PH-LHD and PH-CLD patients decreased pulmonary arterial pulse pressure by 5.6 ± 4.2 mmHg (-12%; p = 0.003) and 4.2 ± 2.2 mmHg (-11%; p < 0.001), increased CPA by 0.4 ± 0.2 ml/mmHg (+23%; p = 0.004) and 0.4 ± 0.3 ml/mmHg (+25%; p = 0.001), and increased right ventricular-to-pulmonary vascular (RV-PV) coupling by 0.24 ± 0.18 (+40%; p = 0.012) and 0.11 ± 0.07 (+21%; p = 0.001), respectively. CONCLUSIONS: Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV-PV coupling.

Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension.

Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription. The primary end point was a composite of all-cause mortality or heart failure (HF) hospitalization. Secondary end points included all-cause mortality, HF hospitalization, and transplant-free survival. Multivariable Cox proportional hazards analyses determined the hazard ratios (HR) and 95% CIs for the primary and secondary end points. Among 205 patients with PAH in the repository, 32.7% (n=67) were on digoxin. Digoxin was more often prescribed to patients with severe PAH and right ventricular failure. After propensity score-matching, 49 patients were digoxin users, and 70 patients were nonusers; of these 31 (63.3%) in the digoxin group and 41 (58.6%) in nondigoxin group met the primary end point during a median follow-up time of 2.1 (0.6-5.0) years. Digoxin users had a higher combined all-cause mortality or HF hospitalization (HR, 1.82 [95% CI, 1.11-2.99]), all-cause mortality (HR, 1.92 [95% CI, 1.06-3.49]), HF hospitalization (HR, 1.89 [95% CI, 1.07-3.35]), and worse transplant-free survival (HR, 2.00 [95% CI, 1.12-3.58]) even after adjusting for patient characteristics and severity of PAH and right ventricular failure. Conclusions In this retrospective, nonrandomized cohort, digoxin treatment was associated with greater all-cause mortality and HF hospitalization, even after multivariate correction. Future randomized controlled trials should assess the safety and efficacy of chronic digoxin use in PAH.

Erythrocyte aging as a mechanism of anemia and a biomarker of device thrombosis in continuous-flow left ventricular assist devices.

BACKGROUND: Blood trauma caused by continuous-flow left ventricular assist devices (CF-LVADs) has been associated with device thrombosis and anemia. Accurate in vivo quantification of erythrocyte turnover and its contribution to CF-LVAD complications have yet to be elucidated. METHODS: We investigated the age (lifespan) of circulating erythrocytes in subjects with CF-LVAD. Erythrocyte lifespan is a quantitative indicator of in vivo erythrocyte turnover that can be accurately derived from measurement of the exhaled carbon monoxide (CO) level. Sixty non-smoking subjects were prospectively enrolled: 25 had a CF-LVAD without thrombosis; 10 had a CF-LVAD with thrombosis; and 25 were normal controls. End-tidal breath CO levels were measured and used to calculate erythrocyte lifespan. RESULTS: The mean erythrocyte lifespan was significantly shorter in CF-LVAD subjects with (29.7 ± 14.9 days) compared to those without (65.0 ± 17.3 days) device thrombosis (p < 0.0001). The lifespans in these 2 groups were significantly shorter compared with normal controls (96.0 ± 24.9 days, both p < 0.0001). A receiver operator curve demonstrated high sensitivity-specificity for use of erythrocyte lifespan to detect device thrombosis (AUC = 0.94). In addition, all CF-LVAD subjects had low hemoglobin (11.8 ± 2.0 g/dl), and their anemia was normochromic normocytic with elevated mean reticulocyte counts. Erythrocyte lifespan correlated significantly with mean corpuscular hemoglobin concentration (r = 0.56, p = 0.0005) and red cell distribution width (r = -0.65, p < 0.001), but not with reticulocyte count (r = 0.27, p = 0.32). CONCLUSIONS: Erythrocyte lifespan is substantially reduced in subjects with a CF-LVAD, which was more pronounced in the presence of device thrombosis. The etiology of anemia in CF-LVAD was primarily due to accelerated erythrocyte aging. Further studies are needed to determine whether erythrocyte lifespan could provide a practical means of detecting subtle pre-clinical thrombosis.

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension.

The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension.

Cardiorenal Syndrome Type 1: Renal Dysfunction in Acute Decompensated Heart Failure.

OBJECTIVE: To present a review of cardiorenal syndrome type 1 (CRS1). METHODS: Review of the literature. RESULTS: Acute kidney injury occurs in approximately one-third of patients with acute decompensated heart failure (ADHF) and the resultant condition was named CRS1. A growing body of literature shows CRS1 patients are at high risk for poor outcomes, and thus there is an urgent need to understand the pathophysiology and subsequently develop effective treatments. In this review we discuss prevalence, proposed pathophysiology including hemodynamic and nonhemodynamic factors, prognosticating variables, data for different treatment strategies, and ongoing clinical trials and highlight questions and problems physicians will face moving forward with this common and challenging condition. CONCLUSION: Further research is needed to understand the pathophysiology of this complex clinical entity and to develop effective treatments.

Is cardiac resynchronization therapy for right ventricular failure in pulmonary arterial hypertension of benefit?

Pulmonary arterial hypertension is a manifestation of a group of disorders leading to pulmonary vascular remodeling and increased pulmonary pressures. The right ventricular (RV) response to chronic pressure overload consists of myocardial remodeling, which is in many ways similar to that seen in left ventricular (LV) failure. Maladaptive myocardial remodeling often leads to intraventricular and interventricular dyssychrony, an observation that has led to cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an effective treatment strategy in subsets of patients with LV failure resulting in improvement in LV function, heart failure symptoms, and survival. Current therapy for pulmonary arterial hypertension is based on decreasing pulmonary vascular resistance, and there is currently no effective therapy targeting the right ventricle or maladaptive ventricular remodeling in these patients. This review focuses on the RV response to chronic pressure overload, its effect on electromechanical coupling and synchrony, and how lessons learned from left ventricular cardiac resynchronization might be applied as therapy for RV dysfunction in the context of pulmonary arterial hypertension.

Cardiovascular risk and psoriasis: beyond the traditional risk factors.

Psoriasis is an autoimmune disease resulting in plaques of the skin. Similar to atherosclerosis, inflammation is integral to the initiation and propagation of plaque development. Mounting evidence has emerged demonstrating that psoriasis not only is associated with increased prevalence of cardiovascular risk factors, but also is an independent risk factor for the development of cardiovascular disease. Systemic therapies for moderate to severe psoriasis can increase the cardiovascular risk. Despite the evidence that psoriasis is an independent risk factor for cardiovascular disease, current guidelines only address managing traditional risk factors. An interdisciplinary approach is needed to find the necessary steps beyond classic risk reduction and detection of early cardiovascular disease in patients with psoriasis, as well as to develop a cardiovascular disease preventive regimen.

Management of vasospastic disorders with botulinum toxin A.

BACKGROUND: Surgical digital artery sympathectomy is indicated when medical management has failed to control rest pain, impending infarction of digits, or healing of ischemic ulcerations caused by profound vasospasm that is associated with other systemic diseases. After digital artery sympathectomy, recurrence or persistence of vasospasm may compromise hand function and ultimately result in amputation of all or portions of both lower and upper extremities. METHODS: The authors present a case series of 11 patients with vasospasm producing intractable rest pain, digital ulcerations, and digit infarctions that failed aggressive medical therapy and that were then treated by perivascular injections of botulinum toxin A (Botox). Before Botox injection, the level of pain, cutaneous temperatures, color, and ulcerations and infarctions were documented RESULTS: The authors' longest follow-up was 30 months. All patients reported highly significant pain reduction, 10 of 10 to 0 to 2 of 10, within 24 to 48 hours after injection, persisting for months after the injection. Nine of 11 patients with nonhealing ulcers spontaneously healed small ulcers and areas of infarction after surgical debridement. Two cases required small skin grafts. Nine of 11 patients reported decreased severity and frequency of vasospastic episodes. CONCLUSIONS: Hand injection of botulinum toxin A appears to be an effective treatment for intractable digital ulcerations and rest pain in patients with severe vasospastic disorders. Because of the complexity of surgical digital artery sympathectomy along with its associated high risk of persistent symptoms, the authors conclude that the therapeutic use of botulinum toxin A injections represents an attractive alternative therapy.

Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial).

OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. METHODS: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.

The case for selective re-issuance of medical certificates to allow pilots who have received a heart transplant to resume flying.

BACKGROUND: Cardiac transplant recipients have been regarded as not medically fit to fly an airplane. Recently, the Federal Aviation Administration decided to re-examine this policy and, in response, this study was undertaken to determine the risk of death from any cause and sudden-onset death in heart transplant recipients during the 12 months after an annual evaluation. METHODS: Of 6,510 patients undergoing primary orthotopic cardiac transplantation enrolled in the Cardiac Transplant Research Database (CTRD), 4,978 patients survived for at least 1 year and formed the basis of this study. Risk factors for death from any causes and sudden-onset death (a composite of causes of death that could conceivably result in a pilot's incapacitation) were determined during the 12-month period after an anniversary evaluation. Patients were re-entered into the analysis at each evaluation, resulting in a total of 23,575 anniversary evaluations. RESULTS: The presence of coronary allograft vasculopathy (CAV), left ventricular systolic dysfunction, history of rejection, malignancy, infection and pre-transplant insulin-dependent diabetes were associated with an increased risk of death from any cause and sudden-onset death during the 12-month period after an evaluation. Based on the absence of these risk factors, a group of heart transplant recipients could be defined with a 12-month risk of death from any cause of 1.0% and of sudden-onset death of 0.3% (which is identical to the mortality rate of a matched population from the U.S. life-table). CONCLUSION: Using these identified risk factors, a group of heart transplant recipients can be defined that are potentially medically certifiable to fly without compromising aviation safety.

Acute renal failure and intravenous immune globulin: occurs with sucrose-stabilized, but not with D-sorbitol-stabilized, formulation.

OBJECTIVE: To report 2 cases of acute renal failure (ARF) following administration of sucrose-stabilized intravenous immune globulin (IVIG), one of which did not recur following subsequent doses of d-sorbitol-stabilized formulation, and review the relevant literature. CASE SUMMARIES: A 44-year-old white man awaiting heart transplantation developed ARF requiring hemodialysis following administration of sucrose-stabilized IVIG for high alloreactivity to population human leukocyte antigens. Following a return of renal function to baseline, subsequent doses of d-sorbitol-stabilized IVIG were administered without incident. A 90-year-old white man developed ARF after administration of sucrose-stabilized IVIG for monoclonal gammopathy. Renal function returned to baseline, and no subsequent IVIG doses were administered. An objective causality assessment revealed that sucrose-stabilized IVIG was the probable cause of the adverse drug event for both cases. DISCUSSION: Several case reports of ARF secondary to IVIG have been published. Recent publications note that sucrose-stabilized IVIG products have a disproportionately high rate of ARF occurrence (approximately 88%) versus non-sucrose-stabilized formulations. Recent market data for IVIG products indicate that sucrose-stabilized products account for approximately 40% of the total IVIG market. When administered intravenously, sucrose is excreted unchanged in the urine. ARF has been reported in patients receiving large doses of intravenous sucrose. CONCLUSIONS: ARF secondary to IVIG may be more likely to occur with sucrose-stabilized formulations. Before prescribing IVIG, clinicians should consider other nephrotoxic medications, preexisting renal function, age, diabetes mellitus, and rate of infusion. In patients at risk, it may be best to avoid sucrose-stabilized formulations.