Emergencies in Pulmonary Hypertension.

Pulmonary hypertension is a challenging disease entity with various underlying etiologies. The management of patients with pulmonary arterial hypertension (WHO Group 1) remains challenging especially in the critical care setting. With risk of high morbidity and mortality, these patients require a multidisciplinary team approach at a speciality care facility for pulmonary hypertension for comprehensive evaluation and rapid initiation of treatment. For acute decompensated right heart failure, management should concentrate on optimizing preload and after load with use of pulmonary vasodilator therapy. A careful evaluation of specialized situations is required for appropriate treatment response.

Evaluation of enoxaparin for bridging of warfarin in outpatients with left ventricular assist devices (LVADs).

BACKGROUND: Patients with left ventricular assist devices (LVADs) require systemic anticoagulation. The use of enoxaparin for bridging to warfarin remains understudied in this population. METHODS: This single-center retrospective study was performed to characterize enoxaparin use and associated thrombotic and bleeding outcomes in adult outpatients with LVADs from January 2018 to July 2021. RESULTS: Fifty-four enoxaparin bridging events were evaluated in 49 patients. Most patients with HeartMate II (HM2) and HeartWare (HVAD) devices received enoxaparin dosed 1 mg/kg every 12 h. In patients with HeartMate 3 (HM3) devices, an equal number of patients received 0.5 mg/kg every 12 h and 1 mg/kg every 12 h, with a smaller subset receiving intermediate doses. The median duration of bridging was 6 days (4-8 [IQR]). One major bleeding event required discontinuation of enoxaparin and hospitalization in a patient with an HM3 device. Thrombotic events occurred in four patients with two incidents of pump thrombosis requiring pump exchange and two ischemic strokes. All thrombotic events occurred in patients with HVAD or HM2 devices. CONCLUSION: These results suggest that enoxaparin bridging in LVAD patients was well-tolerated with low bleeding and thrombotic rates, particularly with the HM3 device.

Significance of Pulmonary Hypertension in Cardiac Amyloidosis.

Pulmonary hypertension (PH) portends a poor prognosis in chronic heart failure and within distinct cardiomyopathies. There is a paucity of data on the impact of PH in patients with light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis (CA). We sought to define the prevalence and significance of PH and PH subtypes in CA. We retrospectively identified patients with a diagnosis of CA who underwent right-sided cardiac catheterization (RHC) from January 2000 to December 2019. PH was defined as mean pulmonary artery pressure >20 mm Hg. PH was phenotyped as precapillary PH (PC-PH; pulmonary capillary wedge pressure [PCWP] <15, pulmonary vascular resistance [PVR] ≥3), isolated postcapillary PH (IpC-PH; PCWP >15, PVR <3), and combined postcapillary and precapillary PH (CpC-PH; PCWP >15 and PVR ≥3). Survival was assessed in those with CA and PH and for PH phenotypes. A total of 132 patients were included, 69 with AL CA and 63 with ATTR CA. A total of 75% (N = 99) had PH (76% of patients with AL and 73% of patients with ATTR, p = 0.615) and the predominant PH phenotype was IpC-PH. The degree of PH was comparable between ATTR CA and AL CA, and PH was observed in advanced stage disease (National Amyloid Center or Mayo stage II or greater). The overall survival for patients with CA and PH was similar to to those without PH. Higher mean pulmonary artery pressure independently predicted mortality in CA with PH (odds ratio 1.06, confidence interval 1.01 to 1.12, p = 0.03). In conclusion, PH was seen frequently in CA and tended to be IpC-PH; however, its presence did not significantly impact survival.

Hemodynamic Profiling and Prognosis in Cardiac Amyloidosis.

BACKGROUND: Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes. METHODS: Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m2), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed. RESULTS: A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98-1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96-1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26-2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01-1.66]) performed better to detect worse outcome (P<0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (P<0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate. CONCLUSIONS: Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.

Novel devices for managing heart failure.

PURPOSE OF REVIEW: Despite advances in heart failure (HF) therapies, the associated morbidity, mortality, hospitalization rates, and healthcare expenditures remain high. A significant proportion of patients with HF remain symptomatic despite receiving optimal medical therapy. Consequently, there exists a large unmet clinical need for novel therapies for treating acute and chronic HF. With the exponential growth of transcatheter interventions in structural heart disease, novel applications of minimally invasive, device-based therapies have been sought in an effort to bridge this treatment gap. The rationale, development, and current data underscoring these therapies will be summarized in this review. RECENT FINDINGS: Recent studies have demonstrated the safety and efficacy of devices that alter left ventricular geometry (i.e., ventriculoplasty), create anatomic shunts to decompress the left atrium, and modulate vena caval and renal blood flow. However pivotal large trials evaluating clinical outcomes are ongoing. SUMMARY: Innovative device-based therapies may expand our armamentarium against the growing heterogeneous and morbid HF syndrome.

Clinical, functional and prognostic implications of severe atrial dilation in secondary mitral regurgitation.

OBJECTIVE: Atrial dilation is known to be a poor prognostic indicator. However, its clinical, functional and prognostic implications have not been thoroughly explored in secondary mitral regurgitation (SMR). We sought to describe the implications of severe atrial dilation (SAD) in SMR. METHODS: We included all adult patients with severe SMR due to left ventricle dysfunction (with no organic mitral valve disease) who underwent transthoracic echocardiography between January 2012 and March 2021 at our institution. The concomitant presence of severe left atrial (LA) dilation (>48 mL/m2) defined SADMR (SAD in SMR), and these patients were compared with those without SAD. RESULTS: A total of 2011 patients were included (mean age 70% and 41% females), with 71% having SADMR. MR severity and ejection fraction were similar between both groups. Patients with SADMR were older, less females and had more diabetes, but similar rates of atrial fibrillation. Mechanistically, they had lower A wave velocity (0.61 vs 0.72 cm/sec, p<0.001) and more impaired LA reservoir strain (9.7% vs 15.5%, p<0.001). Geometrically, SADMR had shallower leaflets' angulations, lower tenting height, larger annuli and smaller leaflet length/annular diameter ratios (all p<0.001). They underwent fewer MV interventions, although these were associated with better outcomes (log-rank p<0.001). Over the study period, SAD was an independent predictor of mortality (HR 1.26, p=0.04). CONCLUSION: SADMR is associated with specific mechanistic and functional alterations and confers a worse prognosis.

Diabetes and Heart Failure: A Marriage of Inconvenience.

Type 2 diabetes and congestive heart failure are growing public health problems and are expected to worsen in the next decade. There is an inarguable link between diabetes and heart failure but only recently has there been an effort to elucidate the underlying pathophysiologic connection resulting in diabetic cardiomyopathy. Traditionally, diabetes and heart failure have been treated as 2 distinct disease entities, but recent advances in individual therapies have shown remarkable concomitant improvements in both diabetes and cardiovascular outcomes. This article aims to review the key connections in the epidemiology and etiopathophysiology of type 2 diabetes and heart failure.

Pharmacokinetic evaluation of treprostinil (oral) for the treatment of pulmonary arterial hypertension.

INTRODUCTION: This review summarizes current information on the first oral prostanoid approved for treatment of pulmonary arterial hypertension, treprostinil diolamine , which, similar to other prostacyclin analogs, vasodilates, impacts remodeling (antiproliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (antithrombotic) and increases right heart inotropy. AREAS COVERED: From a pharmacological point of view, it appears that with sustained blood concentrations for 8 - 10 h after a single dose, twice or thrice daily dosing is possible. This review discusses three randomized trials of oral treprostinil that have been completed (FREEDOM-M, FREEDOM-C, FREEDOM-C2). FREEDOM-C and -C2 evaluated oral treprostinil in patients on stable background therapy; FREEDOM-M evaluated oral treprostinil as monotherapy. In FREEDOM-M, the primary end point (6-minute walk distance; 6MWD) was attained, but was not reached in either FREEDOM-C trial. As such, the FDA did not grant approval. Thus, another clinical trial (FREEDOM-EV) is underway: oral treprostinil in patients on background therapy evaluating co-primary end points: i) change in 6MWD; and ii) occurrence of predetermined events. In the interim, oral treprostinil was approved in December 2013. EXPERT OPINION: The use and future of oral treprostinil is not clear. This will depend on the ability to titrate the drug to high levels with acceptable tolerance, on the results of FREEDOM-EV trial and on the impact of selexipag and other oral prostanoids being developed.