Deborah E. Meyers

A Prospective, Multicenter Trial of the VentrAssist Left Ventricular Assist Device for Bridge to Transplant : Safety and Efficacy

BACKGROUND The increasing prevalence of chronic heart failure has stimulated the ongoing development of left ventricular assist devices (LVADs) for both bridge-to-transplant (BTT) and destination therapy (DT). The aim of this prospective, multicenter clinical trial was to determine the efficacy and safety of a third-generation LVAD, the VentrAssist, in a BTT cohort. METHODS Patients (n = 33) with end-stage chronic heart failure who required circulatory support as BTT therapy were implanted with a VentrAssist device. The primary outcome was survival until transplant or transplant eligibility with the device in situ at trial end-point (Day 154 after implant). The secondary outcomes were pump flow index and end-organ function. Safety, patient functional status and resource use were also assessed. RESULTS At trial end-point, the success rate was 82% (39.4% transplanted, 42.4% transplant-eligible). The LVAD pump flow index (median >or=2.7 liters/min/m(2)) was sufficient to maintain an adequate circulation and significantly improve end-organ function. Of the 77 protocol-defined serious adverse events, most occurred within 30 days of implantation. No patients died as a direct result of pump failure or malfunction. After implantation, patient functional status improved, with 70% of patients achieving hospital discharge, and resource use was reduced. CONCLUSIONS This trial demonstrated a favorable efficacy and safety profile for use of the VentrAssist LVAD in BTT patients.

Arg389Gly-[beta]1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol

Objective Administration of the &bgr;-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both &bgr;1-adrenergic and &bgr;2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. Methods We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50–100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype &bgr;1-adrenergic and &bgr;2-adrenergic receptor polymorphisms. Results When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-&bgr;1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other &bgr;1-adrenergic and &bgr;2-adrenergic receptor polymorphisms (P>0.05). Conclusion In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-&bgr;1 adrenergic receptor phenotype.

Controversies Regarding the Effects of Growth Hormone on the Heart

Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult patients with GH deficiency (GHD) and GH excess (acromegaly) provide important models in which to understand the effects of GH in adult cardiac physiology. An increasing body of clinical and experimental evidence illustrates the specific physiological abnormalities that are likely associated with the excess cardiovascular mortality observed in both acromegaly and GHD. Because human GH replacement is now available to treat adults with GHD, new questions emerge about the long-term cardiovascular effects of replacement therapy. In multiple trials, GH therapy for congestive heart failure has been proved ineffective in the absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH therapy can exert a potent beneficial effect on congestive heart failure. Long-term studies addressing cardiovascular morbidity and mortality are needed to assess the role of GH therapy for GHD.

Exercise training in recently hospitalized heart failure patients enrolled in a disease management programme: design of the EJECTION-HF randomized controlled trial

The Exercise Joins Education: Combined Therapy to Improve Outcomes in Newly‐discharged Heart Failure (EJECTION‐HF) study will evaluate the impact of a supervised exercise training programme (ETP) on clinical outcomes in recently hospitalized heart failure patients attending a disease management programme (DMP).

Present-Day Hospital Readmissions after Left Ventricular Assist Device Implantation: A Large Single-Center Study.

Left ventricular assist device (LVAD) therapy improves survival, hemodynamic status, and end-organ perfusion in patients with refractory advanced heart failure. Hospital readmission is an important measure of the intensity of LVAD support care. We analyzed readmissions of 148 patients (mean age, 53.6 ± 12.7 yr; 83% male) who received a HeartMate II LVAD from April 2008 through June 2012. The patients had severe heart failure; 60.1% were in Interagency Registry for Mechanically Assisted Circulatory Support class 1 or 2. All patients were observed for at least 12 months, and readmissions were classified as planned or unplanned. Descriptive and multivariate regression analyses were used to identify predictors of unplanned readmission. Twenty-seven patients (18.2%) had no readmissions or 69 planned readmissions, and 121 patients (81.8%) had 460 unplanned readmissions. The LVAD-related readmissions were for bleeding, thrombosis, and anticoagulation (n=103; 49.1%), pump-related infections (n=60; 28.6%), and neurologic events (n=28; 13.3%). The readmission rate was 2.1 per patient-year. Unplanned readmissions were for comorbidities and underlying cardiac disease (54.3%) or LVAD-related causes (45.7%). In the unplanned-readmission rate, there was no significant difference between bridge-to-transplantation and destination-therapy patients. Unplanned readmissions were associated with diabetes mellitus (odds ratio [OR]=3.3; P=0.04) and with shorter mileage from residence to hospital (OR=0.998; P=0.046). Unplanned admissions for LVAD-related sequelae and ongoing comorbidities were common. Diabetes mellitus and shorter distance from residence to hospital were significant predictors of readmission. We project that improved management of comorbidities and of anticoagulation therapy will reduce unplanned readmissions of LVAD patients in the future.

Missense mutations in FBN1 exons 41 and 42 cause Weill–Marchesani syndrome with thoracic aortic disease and Marfan syndrome

Mutations in FBN1 cause a range of overlapping but distinct conditions including Marfan syndrome (MFS), Weill–Marchesani syndrome (WMS), familial thoracic aortic aneurysms/dissections (FTAAD), acromicric dysplasia (AD), and geleophysic dysplasia (GD). Two forms of acromelic dysplasia, AD and GD, characterized by short stature, brachydactyly, reduced joint mobility, and characteristic facies, result from heterozygous missense mutations occurring in exons 41 and 42 of FBN1; missense mutations in these exons have not been reported to cause MFS or other syndromes. Here we report on probands with MFS and WMS who have heterozygous FBN1 missense mutations in exons 41 and 42, respectively. The proband with WMS has ectopia lentis, short stature, thickened pinnae, tight skin, striae atrophicae, reduced extension of the elbows, contractures of the fingers and toes, and brachydactyly and has a missense mutation in exon 42 of FBN1 (c.5242T>C; p.C1748R). He also experienced a previously unreported complication of WMS, an acute thoracic aortic dissection. The second proband displays classic characteristics of MFS, including ectopia lentis, skeletal features, and aortic root dilatation, and has a missense mutation in exon 41 of FBN1 (c.5084G>A; p.C1695Y). These phenotypes provide evidence that missense mutations in exons 41 and 42 of FBN1 lead to MFS and WMS in addition to AD and GD and also suggest that all individuals with pathogenic FBN1 mutations in these exons should be assessed for thoracic aortic disease and ectopia lentis. Further studies are necessary to elucidate the factors responsible for the different phenotypes associated with missense mutations in these exons of FBN1.

Protocol-Driven Allied Health Post-Discharge Transition Clinic to Reduce Hospital Readmissions in Heart Failure.

Background Heart failure (HF) patients have high rates of hospitalization and rehospitalization. Methods and Results A protocol‐driven clinic staffed by an allied health care team was designed for patients discharged from the hospital with a diagnosis of congestive HF. The clinic provided follow‐up visits 1 week and 4 to 6 weeks after hospital discharge. One‐hundred and fourteen patients were observed at least 1 time, and 80% of these patients completed the 2‐visit protocol. Clinical evaluations were provided by a nurse practitioner specializing in HF and a clinical pharmacist; these evaluations included physical examination, laboratory evaluation, medical education and reconciliation, medication adjustment and titration, and care coordination. Referrals to home health and appropriate services were provided. At visit 1, 25% of patients were hypervolemic and 13% were hypovolemic. At visit 2, 20% were hypervolemic and 13% were hypovolemic. Medicine reconciliation errors were common, with an average of 2.1 and 0.8 errors per person recorded for visits 1 and 2, respectively. Clinic participants showed a 44.3% reduction in 30‐day readmission rates, as compared to the hospitals average 30‐day readmission rates. Conclusions Protocol‐driven postdischarge transition care delivered by allied health staff addressed multiple transition issues and was associated with a dramatic reduction in readmission rates.

Fatal Cardiac and Renal Allograft Rejection With Lenalidomide Therapy for Light-Chain Amyloidosis

We describe a patient who underwent a successful heart and kidney transplant for light‐chain amyloidosis. She had an excellent hematologic response to bortezomib/dexamethasone therapy. Follow‐up therapy with lenalidomide was started, and the patient quickly had a fatal allograft rejection of the heart and kidney. We present evidence to support the theory that lenalidomide, a known immunomodulator, may have stimulated the immune system and precipitated the fatal rejection episode.

Trauma in Patients With Continuous-Flow Left Ventricular Assist Devices

Trauma-related failure of a continuous-flow left ventricular assist device (LVAD) has not previously been reported. We present 4 cases in which LVAD complications were likely caused by external trauma and led to failure of a HeartMate II device. In 1 case, the onset of symptoms was delayed and the patient did not seek medical attention until months after the traumatic event. All 4 patients required surgical intervention, and 1 patient died of respiratory complications several months postoperatively. In conclusion, a history of external trauma should be considered as a possible etiologic factor when LVAD-supported patients in previously stable condition present with device malfunction.