New Drugs You Are Going to Read About: Serelaxin, Ularitide, TRV027.

Nitrovasodilators have long been used as first-line treatment for hypertensive acute heart failure (AHF). Although effective for BP control and symptom alleviation, this class of agents has never been shown to improve mortality or prevent hospital readmissions. Consequently, there has been tremendous interest in development of newer vasodilators with more beneficial therapeutic profiles. In this review, we focus on three of the most promising agents currently being studied: serelaxin, ularitide, and TRV027. While regulatory approval has yet to be obtained, should they prove beneficial in on-going trials, we are looking at a new era of drug therapy that could supplant more conventional treatments and broaden the horizon for management of patients with AHF.

The pathophysiology of hypertensive acute heart failure.

While acute heart failure (AHF) is often regarded as a single disorder, an evolving understanding recognises the existence of multiple phenotypes with varied pathophysiological alterations. Herein we discuss hypertensive AHF and provide insight into a mechanism where acute fluid redistribution is caused by a disturbance in the ventricular-vascular coupling relationship. In this relationship, acute alterations in vascular elasticity, vasoconstriction and reflected pulse waves lead to increases in cardiac work and contribute to decompensated LV function with associated subendocardial ischaemia and end-organ damage. Chronic predisposing factors (neurohormonal activity, nitric oxide insensitivity, arterial stiffening) and physiological stressors (sympathetic surge, volume overload, physical exertion) that are causally linked to acute symptom onset are discussed. Lastly, we review treatment options including both nitrovasodilators and promising novel therapeutics, and discuss future directions in the management of this phenotypic variant.

Survival after repair of pararenal and paravisceral abdominal aortic aneurysms.

OBJECTIVE: The objective of this study was to review our 27-year clinical experience with open proximal abdominal aortic aneurysm repairs, with a focus on long-term survival. METHODS: A retrospective cohort study was undertaken of all patients who underwent proximal abdominal aortic aneurysm repair between 1986 and 2013 at a tertiary care referral center. Demographics, operative variables, complications, and 30-day mortality were analyzed. Postoperative acute kidney injury was analyzed by the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease)/Acute Kidney Injury Network criteria. Long-term survival was assessed through review of electronic medical records and the Social Security Death Index. Associations between demographics and complications were investigated to determine predictors of long-term survival. RESULTS: The study identified 245 patients. Mean age was 71 years (range, 38-92 years); 69% were men, and 88% were white. Aneurysm type was juxtarenal in 127 patients (52%), suprarenal in 68 patients (28%), and type IV thoracoabdominal in 50 patients (20%). In-hospital mortality was 3.3% (eight patients), and 30-day mortality was 2.9% (seven patients). At least one major complication occurred in 64% of the patients, which included the following: acute kidney injury, 60% (persistent acute kidney injury at discharge, however, was 28%, and hemodialysis at discharge was 1.6%); major pulmonary complications, 22%; myocardial infarction, 4%; visceral ischemia, 2%; and paraplegia, 0.5%. Median follow-up was 54 months. Kaplan-Meier survival estimates were 70% at 5 years and 43% at 10 years. Variables associated with poorer survival included congestive heart failure (hazard ratio [HR], 3.5; P < .001), chronic obstructive pulmonary disease (HR, 1.8; P < .002), and increased aneurysm size at presentation (HR, 1.1; P < .013). Persistent stage 3 acute kidney injury was associated with poor long-term survival. CONCLUSIONS: Open surgical repair of proximal abdominal aortic aneurysms can be performed with low mortality. Acute kidney injury is the most frequent complication, but the need for hemodialysis at discharge is low. Long-term survival is favorable. These data should assist in establishing benchmarks for endovascular repair of complex proximal abdominal aortic aneurysms.