Snehal R. Patel

Combining neurohormonal blockade with continuous-flow left ventricular assist device support for myocardial recovery: A single-arm prospective study

BACKGROUND Combining mechanical unloading by a continuous-flow left ventricular assist device (CF-LVAD) and neurohormonal blockade with heart failure medications (HFMED) is an underexplored clinical strategy to promote recovery of cardiac function in patients with advanced heart failure (HF). METHODS We implemented a clinical protocol to achieve maximal neurohormonal blockade after placement of a CF-LVAD and assessed its utility in an LVAD weaning (6,200 rpm) study. Thirty-four subjects were enrolled after CF-LVAD and were managed with aggressive, bi-weekly up-titration of HFMED. RESULTS Twenty-one subjects (8 with coronary artery disease, 13 with idiopathic dilated cardiomyopathy) were included in this LVAD weaning investigation. Overall, combined CF-LVAD and HFMED resulted in significant reverse remodeling with a decrease in left atrial volume index (44.7±16.0 to 31.6±12.1 ml/m(2), p < 0.001) and LV internal diastolic diameter (6.7±1.5 to 6.0±1.6 cm, p = 0.003) and an increase in LV ejection fraction (17.4±6.5 to 33.1±16.2%, p < 0.001) during LVAD weaning (6,200 rpm). Five of 21 (24%) subjects demonstrated recovery of biventricular function. Exploratory analysis showed that recovered subjects had shorter duration HF, less myocardial fibrosis and less myocyte hypertrophy, and were supported at higher LVAD speeds. CONCLUSIONS CF-LVAD support in combination with HFMED leads to significant reverse remodeling in patients with advanced HF. Using this approach, one quarter of patients demonstrated complete recovery of cardiac function. Our results suggest that bridge to recovery in the current device era is a clinically meaningful phenomenon and merits further investigation.

Blood Pressure and Adverse Events During Continuous Flow Left Ventricular Assist Device Support

Background—Adverse events (AEs), such as intracranial hemorrhage, thromboembolic event, and progressive aortic insufficiency, create substantial morbidity and mortality during continuous flow left ventricular assist device support yet their relation to blood pressure control is underexplored. Methods and Results—A multicenter retrospective review of patients supported for at least 30 days and ⩽18 months by a continuous flow left ventricular assist device from June 2006 to December 2013 was conducted. All outpatient Doppler blood pressure (DOPBP) recordings were averaged up to the time of intracranial hemorrhage, thromboembolic event, or progressive aortic insufficiency. DOPBP was analyzed as a categorical variable grouped as high (>90 mm Hg; n=40), intermediate (80–90 mm Hg; n=52), and controlled (<80 mm Hg; n=31). Cumulative survival free from an AE was calculated using Kaplan–Meier curves and Cox hazard ratios were derived. Patients in the high DOPBP group had worse baseline renal function, lower angiotensin-converting enzyme inhibitor or angiotensin receptor blocker usage during continuous flow left ventricular assist device support, and a more prevalent history of hypertension. Twelve (30%) patients in the high DOPBP group had an AE, in comparison with 7 (13%) patients in the intermediate DOPBP group and only 1 (3%) in the controlled DOPBP group. The likelihood of an AE increased in patients with a high DOPBP (adjusted hazard ratios [95% confidence interval], 16.4 [1.8–147.3]; P=0.012 versus controlled and 2.6 [0.93–7.4]; P=0.068 versus intermediate). Overall, a similar association was noted for the risk of intracranial hemorrhage (P=0.015) and progressive aortic insufficiency (P=0.078) but not for thromboembolic event (P=0.638). Patients with an AE had a higher DOPBP (90±10 mm Hg) in comparison with those without an AE (85±10 mm Hg; P=0.05). Conclusions—In a population at risk, higher DOPBP during continuous flow left ventricular assist device support was significantly associated with a composite of AEs.

Impact of Adverse Events on Ventricular Assist Device Outcomes

Left ventricular assist devices have been proven to be superior to medical therapy for advanced heart failure patients awaiting heart transplantation and viable alternatives to transplantation for destination therapy patients. Improvements in the design of ventricular assist devices have been rewarded by a decrease in adverse events and an increase in survival. Despite significant progress, even the latest generation left ventricular assist devices are burdened by a significant long-term adverse events profile that will increasingly challenge physicians as patients survive longer on implantable mechanical circulatory support. In this review, we analyze the impact of long-term adverse events on clinical outcomes in the major trials of continuous flow left ventricular assist devices. We discuss several of the more pertinent and interesting adverse events, examine their potential causes, and explore their future implications.

Frailty Assessment in Advanced Heart Failure

BACKGROUND Several studies have recently demonstrated the value of frailty assessment in a general heart failure (HF) population; however, it is unknown whether these findings are also applicable in advanced HF. We investigated the utility of frailty assessment and its prognostic value in elderly patients with advanced HF. METHODS Forty consecutive elderly subjects aged ≥65 years, with left ventricular ejection fraction ≤35%, New York Heart Association class III or IV, and a 6-minute walk test <300 m were enrolled from the HF clinic at Montefiore Medical Center between October 2012 and July 2013. Subjects were assessed for frailty with the Fried Frailty Index, consisting of 5 components: hand grip strength, 15-foot walk time, weight loss, physical activity, and exhaustion. All subjects were prospectively followed for death or hospitalization. RESULTS At baseline, the mean age of the cohort was 74.9 ± 6.5 years, 58% female, left ventricular ejection fraction 25.6 ± 6.4%, 6-minute walk test 195.8 ± 74.3 m and length of follow-up 454 ± 186 days. Thirty-five percent were prefrail and 65% were frail. Frailty status was associated with the combined primary endpoint of mortality and all-cause hospitalization (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.15-3.25, P = .013). On individual analysis, frailty was associated with all-cause hospitalizations (HR 1.92, 95% CI 1.12-3.27, P = .017) and non-HF hospitalizations (HR 3.31, 95% CI 1.14- 9.6, P = .028), but was not associated with HF hospitalizations alone (HR 1.31, 95% CI 0.68-2.49, P = .380). CONCLUSIONS Frailty assessment in patients with advanced HF is feasible and provides prognostic value. These findings warrant validation in a larger cohort.

Watchful Waiting in Continuous-Flow Left Ventricular Assist Device Patients With Ongoing Hemolysis Is Associated With an Increased Risk for Cerebrovascular Accident or Death

Background—Management of hemolysis in the setting of suspected device thrombosis in continuous-flow left ventricular assist device patients varies widely, ranging from watchful waiting with intensified antithrombotic therapy to early surgical device exchange. The aim of this study was to compare the outcomes of hemolysis events treated with surgical interventions versus medical management alone. Methods and Results—A retrospective review of Heartmate II continuous-flow left ventricular assist device patients at 2 centers from January 2009 to September 2014 was completed. Patients were categorized as surgical management if hemolysis refractory to intensification of standard antithrombotic therapy was treated surgically. The primary end point was the first occurrence of cerebrovascular accident (CVA) or death. Sixty-four hemolysis events occurred in 49/367 patients implanted with Heartmate II continuous-flow left ventricular assist devices. Of 49 primary hemolysis events, 24 were treated with surgical interventions. After surgical treatment, 1 patient died and 2 experienced CVAs, as compared with 3 deaths and 9 CVAs in the 25 patients who remained on intensified antithrombotic therapy alone. The 1-year freedom from CVA or death was 87.5% and 49.5% in the surgical and medical cohorts, respectively (P=0.027). Resolution of a primary hemolysis event without CVA or death occurred in 21/24 patients treated with surgical interventions and in 13/25 who remained on medical therapy alone. A similar association between treatment and outcome was noted in the 15 recurrent hemolysis events. Conclusions—Hemolysis refractory to intensification of antithrombotic therapy identifies continuous-flow left ventricular assist device patients at major risk for CVA and death. Early device exchange should be considered to minimize these risks.

Creating adequate pulsatility with a continuous flow left ventricular assist device: just do it!

Purpose of review Continuous flow left ventricular assist devices (LVADs) have revolutionized the treatment of advanced heart failure; however, as experience with these devices has grown, a number of unanticipated adverse events have emerged. In this study, we review the current literature associating a lack of pulsatility with these events. Recent findings It is now evident that continuous flow LVAD physiology reflects a spectrum of ‘low pulsatile’ rather than a truly ‘nonpulsatile’ state. Thus, the detrimental consequences of nonpulsatile flow noted in early experimental setups may or may not occur in humans supported with continuous flow LVADs. Such studies have demonstrated not only alterations in vascular function and structure during continuous flow LVAD support, but also a clear association of the degree of alterations in vascular, baroreceptor, and sympathetic nervous system function with the degree of actual pulsatility. In addition, a number of clinical events have been linked to continuous flow LVAD physiology, including a decreased extent of ventricular unloading possibly impairing myocardial recovery, hemolysis and device thrombosis, development of aortic insufficiency, and mucosal bleeding. Summary Many of the adverse effects of the current continuous flow LVADs are associated with low pulsatile flow. An evolved understanding of pulsatility as a continuous rather than a binary variable may allow us to incorporate appropriate degrees of pulsatility into the next generation pumps and mitigate these effects.

From Acute Decompensated to Chronic Heart Failure

An acute decompensation of heart failure resulting in hospital admission represents a critical juncture in the natural history of the disease, as evidenced by poor mortality and readmission outcomes after hospital discharge. For this reason, a number of new short-term vasoactive therapies have been or are being tested in clinical trials. Furthermore, in response to unacceptable readmission rates, there has been intense interest in improving the transition from hospital discharge to the outpatient arena. Between these 2 areas of focus exists an often overlooked internal transition from acute vasoactive therapies to oral chronic heart failure medications. This transition from acute presentation to the rest of the hospital stay forms the basis of this review.

Antiplatelet Therapy and Adverse Hematologic Events During Heart Mate II Support

Background—Hematologic adverse events are common during continuous flow left ventricular assist device support; yet, their relation to antiplatelet therapy, including aspirin (ASA) dosing, is uncertain. Methods and Results—A single-center retrospective review of all patients supported by a continuous flow left ventricular assist device (Heart Mate II) from June 2006 to November 2014 was conducted. Patients were categorized into 3 groups: (1) ASA 81 mg+dipyridamole 75 mg daily (n=26) with a target international normalized ratio (INR) of 2 to 3 from June 2006 to August 2009; (2) ASA 81 mg daily (n=18) from September 2009 to August 2011 with a target INR of 1.5 to 2; and (3) ASA 325 mg daily from September 2011 to November 2014 with a target INR of 2 to 3 (n=70). Hemorrhagic and thrombotic outcomes were retrieved ⩽365 days after implantation. Cumulative survival free from adverse events was calculated using Kaplan–Meier curves and Cox proportional hazard ratios were generated. Hemorrhagic events occurred in 6 patients on ASA 81 mg+dipyridamole (26%; 0.42 events per patient year; mean INR at event, 2.2), 4 patients on ASA 81 mg (22%; 0.38 events per patient year; mean INR at event, 2.0), and in 38 patients on ASA 325 mg (54%; 1.4 events per patient year; mean INR at event, 2.2); P=0.004. Patients on ASA 325 mg had a higher adjusted hazard ratio of 2.9 (95% confidence interval, 1.2–7.0 versus ASA 81 mg+dipyridamole; P=0.02) and 3.4 (95% confidence interval, 1.2–9.5 versus ASA 81 mg; P=0.02) for hemorrhagic events. Thrombotic events rates were not different between groups. Conclusions—High-dose ASA in Heart Mate II patients treated concomitantly with warfarin is associated with an increased hazard of bleeding but does not reduce thrombotic events.

Outcomes of Restrictive and Hypertrophic Cardiomyopathies After LVAD: An INTERMACS Analysis

BACKGROUND Patients with restrictive (RCM) and hypertrophic (HCM) cardiomyopathies are felt to be a difficult population to treat with left ventricular assist device (LVAD) therapy. Scarce data exist on outcomes of continuous-flow (CF) LVAD support in these challenging patient cohorts. METHODS The Interagency Registry for Mechanically Assisted Circulatory Support Registry was queried for all patients with RCM (n = 94) and HCM (n = 104) who underwent CF LVAD implantation between March 2008 and March 2014. Survival, adverse event rates, baseline demographics, echocardiography parameters, and competing outcomes were compared with patients with dilated cardiomyopathy (DCM) (n = 8749). RESULTS Left ventricular size was smaller and baseline EF was higher in RCM and HCM compared with DCM patients. Nonetheless, these parameters were not completely normal in the RCM and HCM groups, suggesting that most of these patients exhibited features of a DCM and represented a mixed phenotype. In these specific patient populations, survival up to 4 years was not different among the 3 groups (log rank 0.25) and competing outcomes at 1 year were similar. In the subgroup of patients with very small ventricles (ie, < 5.0 cm), survival was far inferior. Finally, overall rates of right ventricular assist device requirement, hemolysis, pump dysfunction, and cardiac arrhythmias were similar among the 3 groups. CONCLUSION Relatively few patients with HCM and RCM undergo CF LVAD implantation, and most that do display some features of a DCM. Overall survival and adverse event profiles of these patients were similar to traditional DCM patients; however, in those with very small ventricles, survival was inferior.

IMPROVED QUALITY OF LIFE SCORES AND EXERCISE CAPACITY WITH REMOTE PULMONARY ARTERY PRESSURE MONITORING IN PATIENTS WITH CHRONIC HEART FAILURE

The impact of remote pulmonary artery pressure (PAP) monitoring on quality of life (QOL) and exercise capacity in outpatients with chronic heart failure is unknown. Sixty six outpatients with NYHA class III heart failure were screened for implantation of a PAP monitoring device, CardioMEMS (CM).