Mavacamten-A Targeted Therapy for Hypertrophic Cardiomyopathy.

ABSTRACT: The pathophysiology of hypertrophic cardiomyopathy is primarily comprised of dynamic left ventricular outflow tract obstruction, mitral regurgitation, and diastolic dysfunction. Symptoms such as dyspnea, angina, or syncope can occur because of left ventricular (LV) hypertrophy and reduced LV cavity size. Currently, focus on symptom relief through optimizing LV preload and reducing inotropy is the mainstay of therapy through the use of ß-blockers, nondihydropyridine calcium channel blockers, and disopyramide. Mavacamten is a novel cardiac myosin inhibitor recently approved by the Food and Drug Administration for the treatment of obstructive hypertrophic cardiomyopathy. Mavacamten normalizes myosin and actin cross-bridging to decrease contractility and ultimately reduce LV outflow tract gradients to maximize cardiac output. In this review, we report on the mechanism of action of mavacamten, safety profile, and phase 2 and 3 clinical trial data. Because of the risk of heart failure resulting from systolic dysfunction, careful patient selection and close monitoring are key for implementing this therapy into cardiovascular practice.

Long-Term Ambulatory Intravenous Milrinone Therapy in Advanced Heart Failure.

BACKGROUND: The role of intravenous (IV) inotropes in the treatment of ambulatory patients with advanced heart failure (HF) remains controversial. METHODS: This was a retrospective study of patients with advanced HF. Patients on home IV milrinone, who remained on it for at least 3 months, were included. We compared the data from 3 months before starting IV milrinone to 3 months after initiating therapy. A subset of patients who remained on milrinone for 6 months or longer was analysed separately. RESULTS: A total of 90 patients remained on continuous IV milrinone for 3 months, and 55 patients were treated for 6 months or longer. In both groups, improvements in cardiac index (1.86-2.25, p<0.001 and 1.9-2.38, p<0.0001), New York Heart Association (NYHA) class (3.32-2.76, p<0.0001 and 3.25-2.72, p=0.001), and liver function were noted. In the 6-month group, there was also a decrease in mean hospitalised days per patient (9.40 vs 4.12, p<0.001) and an improved tolerance of beta blocker therapy (83.3% vs 98.1%, p=0.006). CONCLUSION: Long-term IV use of milrinone is associated with improvement in haemodynamics, functional class, tolerance of medical therapy, and decrease in hospitalised days.

Evaluation of Zoledronate as Treatment for Hypercalcemia in Four Dogs.

Hypercalcemia is a biochemical abnormality that, when left untreated, can lead to life-threatening complications including renal failure. Bisphosphonates are routinely used to treat hypercalcemia, but most literature on veterinary patients describes the use of pamidronate. This retrospective case series describes the use of zoledronate for treatment of hypercalcemia in four dogs. Information including signalment, clinical signs, treatment, and outcome was collected. All dogs showed a decrease in total and ionized calcium concentrations after treatment with zoledronate. All treatments of zoledronate administered were well tolerated, but a previously unreported local hypersensitivity reaction was observed in one dog. This report is the first to document the efficacy of zoledronate for treatment of hypercalcemia in dogs.

Antithromboembolic Strategies for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.

Major anthropogenic causes for and outcomes of wild animal presentation to a wildlife clinic in East Tennessee, USA, 2000-2011.

To determine the reasons for presentation and outcome of wildlife cases in East Tennessee, a retrospective analysis was performed using 14,303 records from cases presented to the wildlife clinic of the University of Tennessee Veterinary Teaching Hospital between 2000 and 2011. The cases were first categorized into amphibian/non-avian reptile, mammal, or avian and then classified into groups based on the primary admitting/presenting sign. There are a variety of reasons animals were presented to the clinic, and some were directly or indirectly anthropogenic in origin, including cat related, dog related, hit by automobile, and other human encounters leading to trauma; of the cases reviewed, 4,443 (31.1%) presented for one of these 4 reasons. Overall case fatality risk in regard to these 4 admitting/presenting signs was 0.519 for the amphibian/non-avian reptile cases, 0.675 for mammal cases, and 0.687 for avian cases. This study confirms the importance of monitoring wildlife morbidity and mortality and of focusing efforts to reduce the anthropogenic threat on native habitats and resident wildlife populations.