A. Reshad Garan

Outcomes after stroke complicating left ventricular assist device

BACKGROUND Stroke is one of the leading complications during continuous flow-left ventricular assist device (CF-LVAD) support. Risk factors have been well described, although less is known regarding treatment and outcomes. We present a large single-center experience on stroke outcome and transplant eligibility by stroke sub-type and severity in CF-LVAD patients. METHODS Between January 1, 2008, and April 1, 2015, 301 patients underwent CF-LVAD (266 HeartMate II [HM I], Thoratec Corp, Pleasanton, CA; 35 HeartWare [HVAD], HeartWare International Inc, Framingham, MA). Stroke was defined as a focal neurologic deficit with abnormal neuroimaging. Intracerebral hemorrhage (ICH) definition excluded sub-dural hematoma and hemorrhagic conversion of an ischemic stroke (IS). Treatment in IS included intra-arterial embolectomy when appropriate; treatment in ICH included reversal of coagulopathy. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). Outcomes were in-hospital mortality and transplant status. RESULTS Stroke occurred in 40 patients: 8 ICH (4 HM II, 4 HVAD) and 32 IS (26 HM II, 6 HVAD). Among 8 ICH patients, there were 4 deaths (50%), with NIHSS of 18.8 ± 13.7 vs 1.8 ± 1.7 in survivors (p = 0.049). Among 32 IS patients, 12 had hemorrhagic conversion and 5 were treated with intra-arterial embolectomy. There were 9 deaths (28%), with NIHSS of 16.2 ± 10.8 vs 7.0 ± 7.6 in survivors (p = 0.011). Among the 32 IS patients, 12 underwent transplant, and 1 is awaiting transplant. No ICH patients received a transplant. CONCLUSIONS In-hospital mortality after stroke is significantly affected by the initial neurologic impairment. Patients with IS appear to benefit the most from in-hospital treatment and often make sufficient recovery to be able to progress to transplant.

The role of implantable cardioverter defibrillators in patients bridged to transplantation with a continuous-flow left ventricular assist device: A propensity score matched analysis

BACKGROUND Implantable cardioverter defibrillators (ICDs) provide a significant mortality benefit for appropriately selected patients with advanced heart failure. ICDs are associated with a mortality benefit when used in patients with a pulsatile left ventricular assist device (LVAD). It is unclear whether patients with a continuous-flow LVAD (CF-LVAD) derive the same benefit. We sought to determine if the presence of an ICD provided a mortality benefit during CF-LVAD support as a bridge to transplantation. METHODS Patients were identified in the United Network for Organ Sharing (UNOS) registry who underwent LVAD implantation as bridge to transplantation between May 2004 and April 2014, with follow-up through June 2014. Primary outcome was freedom from death while on CF-LVAD support with adjustment for complications requiring UNOS listing status upgrade. Secondary end-points included freedom from delisting while on CF-LVAD support and incidence of transplantation. RESULTS The study cohort comprised 2,990 patients, and propensity score matching identified 1,012 patients with similar propensity scores. There was no difference in survival during device support between patients with and without an ICD (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.66-2.17; p = 0.55). Adjusting for device complications requiring a UNOS listing status upgrade had minimal influence (HR = 1.11; 95% CI, 0.60-2.05; p = 0.74). There was no increased risk of delisting owing to being too sick for patients with an ICD (HR = 1.08; 95% CI, 0.63-1.86; p = 0.78). Likewise, the probability of transplantation was similar (HR = 1.05; 95% CI, 0.87-1.27; p = 0.62). CONCLUSIONS Among patients bridged to transplantation with a CF-LVAD, the presence of an ICD did not reduce mortality.

Predictors of survival and ability to wean from short-term mechanical circulatory support device following acute myocardial infarction complicated by cardiogenic shock:

Background: Cardiogenic shock following acute myocardial infarction (AMI-CS) portends a poor prognosis. Short-term mechanical circulatory support devices (MCSDs) provide hemodynamic support for patients with cardiogenic shock but predictors of survival and the ability to wean from short-term MCSDs remain largely unknown. Methods: All patients > 18 years old treated at our institution with extra-corporeal membrane oxygenation or short-term surgical ventricular assist device for AMI-CS were studied. We collected acute myocardial infarction details with demographic and hemodynamic variables. Primary outcomes were survival to discharge and recovery from MCSD (i.e. survival without heart replacement therapy including durable ventricular assist device or heart transplant). Results: One hundred and twenty-four patients received extra-corporeal membrane oxygenation or short-term surgical ventricular assist device following acute myocardial infarction from 2007 to 2016; 89 received extra-corporeal membrane oxygenation and 35 short-term ventricular assist device. Fifty-five (44.4%) died in the hospital and 69 (55.6%) survived to discharge. Twenty-six (37.7%) required heart replacement therapy (four transplant, 22 durable ventricular assist device) and 43 (62.3%) were discharged without heart replacement therapy. Age and cardiac index at MCSD implantation were predictors of survival to discharge; patients over 60 years with cardiac index <1.5 l/min per m2 had a low likelihood of survival. The angiographic result after revascularization predicted recovery from MCSD (odds ratio 9.00, 95% confidence interval 2.45–32.99, p=0.001), but 50% of those optimally revascularized still required heart replacement therapy. Cardiac index predicted recovery from MCSD among this group (odds ratio 4.06, 95% confidence interval 1.45–11.55, p=0.009). Conclusion: Among AMI-CS patients requiring short-term MCSDs, age and cardiac index predict survival to discharge. Angiographic result and cardiac index predict ventricular recovery but 50% of those optimally revascularized still required heart replacement therapy.

The Unique Blood Pressures and Pulsatility of LVAD Patients: Current Challenges and Future Opportunities

An increasing number of end-stage heart failure patients are now implanted with continuous-flow left ventricular assist devices (CF-LVADs). Although this therapeutic approach is associated with improved clinical outcomes, continuous flow physiology reduces arterial pulse pressure and pulsatility to an extent that is unique to this population. Recent data suggest that high blood pressure (BP) contributes to life-threatening complications such as pump thrombosis and stroke of CF-LVAD patients. However, limited understanding of the distinct hemodynamics of these pumps makes measurement and, consequently, medical management of BP quite challenging. Here, we review the evolution of LVAD design, the impact of CF-LVAD flow, and “artificial pulse” technology on hemodynamics and BP measurement, as well as suggest new approaches for the assessment and interpretation of the unique physiology of modern LVADs.

Ventricular Assist Device Utilization in Heart Transplant Candidates: Nationwide Variability and Impact on Waitlist Outcomes

Background: Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard treatment choice in advanced heart failure patients. We hypothesized that practice patterns with regards to CF-LVAD utilization vary significantly among transplant centers and impact waitlist outcomes. Methods and Results: The United Network for Organ Sharing registry was queried to identify adult patients who were waitlisted for heart transplantation (HT) between 2008 and 2015. Each patient was assigned a propensity score based on likelihood of receiving a durable CF-LVAD before or while waitlisted. The primary outcomes of interest were death or delisting for worsening status and HT at 1 year. A total of 22 863 patients from 92 centers were identified. Among these, 9013 (39.4%) were mechanically supported. CF-LVAD utilization varied significantly between and within United Network for Organ Sharing regions. Freedom from waitlist death or delisting was significantly lower in propensity-score–matched patients who were mechanically supported versus medically managed (83.5% versus 79.2%; P<0.001). However, cumulative incidence of HT was also lower in mechanically supported patients (53.3% versus 63.6%; P<0.001). Congruous mechanical and medical bridging strategies based on clinical risk profile were associated with lower risk of death or delisting (hazard ratio, 0.88; P=0.027) and higher likelihood of HT (hazard ratio, 1.14; P<0.001). Conclusions: CF-LVAD utilization may lower waitlist mortality at the expense of lower likelihood of HT. Decision to use CF-LVAD and timing of transition should be individualized based on patient-, center-, and region-level risk factors to achieve optimal outcomes.

Non-invasive measurement of peripheral, central and 24-hour blood pressure in patients with continuous-flow left ventricular assist device

This article was published in The Journal of Heart and Lung Transplantation on 05 March 2017 (online), available at http://dx.doi.org/10.1016/j.healun.2017.02.026

Discriminatory performance of positive urine hemoglobin for detection of significant hemolysis in patients with continuous-flow left ventricular assist devices.

BACKGROUND Serum lactate dehydrogenase (LDH) is the standard measure for detection of hemolysis and thus surveillance for device thrombosis in patients on continuous-flow left ventricular assist device (CF-LVAD) support. Significant hemolysis has been defined as LDH ≥600 IU/L. However, LDH testing requires phlebotomy, precluding frequent home monitoring. Simple dipstick urinalysis (UA) for urine hemoglobin (U-Hb) overcomes this limitation. This study correlated U-Hb and LDH levels and evaluated the performance of UA for detection of significant hemolysis in patients with CF-LVADs. METHODS U-Hb and LDH were measured concurrently 956 times in 221 patients with CF-LVADs. Statistics were computed to determine accuracy of UA in detecting LDH ≥600 IU/L, with a positive result being any detected U-Hb. All analyses were performed with and without excluding for 1) conditions associated with tissue damage, which are known to increase LDH, and 2) suspected or confirmed urinary tract infections or hematuria, which are known to cause hemoglobinuria for reasons other than hemolysis. RESULTS Mean LDH for absent/mild/severe U-Hb was 360 IU/L/467 IU/L IU/L/777 IU/L without exclusions, 354 IU/L/444 IU/L IU/L/651 IU/L after excluding non-hemolytic LDH elevations, 370 IU/L/513 IU/L IU/L/1,357 IU/L after excluding urinary tract infections and hematuria, and 367 IU/L/470 IU/L IU/L/1,217 IU/L when both exclusions applied (all p < 0.001). Absent U-Hb had a negative predictive value for LDH ≥600 IU/L of >90% for all analyses. CONCLUSIONS Serum LDH is significantly associated with U-Hb levels. Absence of U-Hb appears to efficiently exclude significant hemolysis in patients with CF-LVADs. Because it can be performed by patients at home, hemoglobinuria monitoring may enable more intense surveillance and earlier diagnosis of device thrombosis.

Combined Therapy of Ventricular Assist Device and Membrane Oxygenator for Profound Acute Cardiopulmonary Failure

Short-term ventricular assist devices (ST-VADs) have been effective in treating the patients with refractory cardiogenic shock. Membrane oxygenators (MOs) can be added to the circuit for concomitant, profound refractory hypoxia. This study reports the outcomes of combined therapy in this portion of patients. This is a retrospective review of 166 patients who received an ST-biventricular assist device (BiVAD) or right ventricular assist device (RVAD) for cardiogenic shock between November 2007 and November 2014. An MO was added to the RVAD for profound hypoxia refractory to maximized ventilation. Patients were divided into two groups: 33 with (MO-VAD [MV]) and 133 without (VAD only [VO]) an MO. Survival to discharge and adverse events were compared between groups. More MV than VO patients were intubated (93.9% vs. 59.4%; p < 0.001) and on veno-arterial extracorporeal membrane oxygenator (VA-ECMO) (72.7% vs. 19.5%; p < 0.001) before implantation. Survival to discharge (51.5% MV vs. 52.6% VO; p = 0.515) and 1 year survival (54.4% MV vs. 48.6% VO; p = 0.955) were not significantly different. MV patients had more prolonged intubation (69.7% vs. 37.6%; p < 0.001), tracheostomies (39.4% vs. 16.5%; p = 0.008), and a higher risk for bleeding (p = 0.037). Patients suffering from cardiogenic shock with refractory hypoxia requiring combined ST-VAD and MO therapy appear to achieve similar mid-term survival despite increased risk for early complications.

Cardiogenic Shock in Older Adults

Cardiogenic shock, a shock state with underlying cardiovascular insult as the precipitating event, carries a high mortality irrespective of the actual inciting pathology. This remains one disease entity in cardiovascular medicine that has not seen vast improvements over the past several decades. With the exception of the realization of the importance of early revascularization in the setting of acute myocardial infarction, there have been few breakthroughs in the treatment of this devastating condition. How to optimize outcomes for older adults with cardiogenic shock is an even more challenging task as the studies in this field have largely failed to include this patient demographic. Mechanical circulatory support devices hold great promise to improve outcomes for this condition, though their invasive nature and high rate of complications raise concern over their use in older patient populations.