Justin Fried

Aortic stenosis and coronary artery disease: What do we know? What don't we know? A comprehensive review of the literature with proposed treatment algorithms

Aortic valve stenosis is the most common form of valvular heart disease in the elderly population and occurs frequently in conjunction with coronary artery disease. The standard treatment option for patients with these two conditions has been surgical aortic valve replacement and coronary artery bypass grafting. The arrival of transcatheter aortic valve replacement has considerably shifted the treatment paradigms. Nevertheless, a lot of questions remain unanswered regarding the management of coronary artery disease in the setting of the transcatheter options for severe aortic stenosis. This article includes a comprehensive review of the literature and seeks to describe the actual knowledge on the topic of aortic stenosis and concomitant coronary artery disease.

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.

Continuous-flow left ventricular assist devices and usefulness of a standardized strategy to reduce drive-line infections

BACKGROUND Drive-line infection (DLI) is a common complication of left ventricular assist device (LVAD) support, leading to significant morbidity that jeopardizes the benefits of these devices. It has been reported that DLI incidence is related to drive-line dressing strategies. The aim of this study was to determine whether implementation of a standardized drive-line care kit would reduce the incidence of DLIs. METHODS DLI data were collected prospectively on all LVAD patients implanted between 2009 and 2013 at Columbia University Medical Center. Drive-line care was altered on June 1, 2011, from a dry sterile dressing without a standard anchoring device to a standardized kit, which included silver gauze dressing and a standard anchoring device. The silver dressing was used until the wound incorporated, with a minimum of 1 month. RESULTS During the study period, 107 patients were implanted with LVADs before implementation of a standardized kit (Group A) and 159 thereafter (Group B). Median follow-up time (censoring at June 2011) for Group A was 8.73 (IQR 3.51 to 17.47) months and 11.65 (IQR 6.66 to 35.20) months for Group B (p = 0.17). DLI event rate improved from 0.18 to 0.07 event per patient-year, corresponding to a relative risk reduction of 62.5%. In addition, the 1-year freedom from infection was significantly increased in Group B (92.46%) compared with Group A (81.94%) (log rank = 0.036). CONCLUSION The use of a standardized kit, including silver dressing and a standard anchoring device, leads to decrease in DLI with an absolute risk reduction of 11%. Routine use of these dressing techniques is warranted based on our findings, and may lead to reduction of complications related to infections.

Incidence and predictors of myocardial recovery on long-term left ventricular assist device support: Results from the United Network for Organ Sharing database

BACKGROUND Mechanical circulatory support (MCS) leads to favorable changes in the failing heart at the molecular, cellular, and structural levels. However, myocardial recovery leading to device explantation is rare. We reasoned that the multicenter United Network for Organ Sharing (UNOS) registry might provide insights into clinical predictors and outcomes of the recovery process. METHODS The MCS device data set of the UNOS registry was queried for patients with long-term continuous-flow left ventricular assist devices (CF-LVADs) that were explanted for heart transplantation or indication of recovery. Analysis was restricted to adult patients (≥18 years old) who were listed for an initial heart transplantation. Patients with CF-LVADs that were explanted because of recovery were compared with patients with CF-LVADs who underwent transplantation. RESULTS We identified 594 patients with HeartMate II devices and 92 patients with HeartWare devices. Duration of support was on average 500.4 ± 325.3 days. In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery. Univariate predictors of recovery in patients with long-term LVADs included younger age (40 years vs 53 years), female sex, lower body mass index (25.7 kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation period, freedom from death or transplantation was 66% at 1 year. CONCLUSIONS The incidence of recovery on device support is low in the current MCS era and limited to a select cohort of predominantly young patients with non-ischemic myopathy. Given the high incidence of disease recurrence, patients should be closely followed after device explantation.

Prior hematologic conditions carry a high morbidity and mortality in patients supported with continuous-flow left ventricular assist devices

BACKGROUND Mechanical support leads to an increased risk of both bleeding and thrombotic events, but little is known about the risk of device support in patients with a baseline predisposition to these events. The aim of this study was to examine outcomes among patients with baseline hematologic conditions who underwent continuous-flow LVAD implantation (CF-LVAD). METHODS We retrospectively reviewed records of 286 patients who underwent CF-LVAD implantation at the Columbia University Medical Center between April 2008 and December 2013. Patients diagnosed with the following hematologic conditions were enrolled: idiopathic thrombocytopenic purpura (ITP); Factor V Leiden; elevated Factor VIII; heparin-induced thrombocytopenia (HIT); or undefined hypercoagulable state. RESULTS Of the 286 CF-LVAD patients implanted during the study period, 12 were considered to have a significant hematologic condition predisposing them to either bleeding or thrombotic events. The study included 5 patients with ITP, 1 with Factor V Leiden, 1 with elevated Factor VIII, 2 with HIT and 3 patients with undefined hypercoagulable state. Patients were supported for a total of 168.46 months, with a median of 10.76 months (IQR 4.78 to 21.36 months). There was a high frequency of thrombotic (0.57 event per patient-year), neurologic (0.36 event per patient-year) and bleeding (0.64 event per patient-year). Actuarial survival rates at 6 and 12 months were 81.8%, but fell to 49% at 2 years. CONCLUSIONS Patients with a history of prior hematologic conditions are at high risk for bleeding, thrombotic and neurologic events during device support, leading to early mortality. This case series questions the benefit of CF-LVAD in these patients and the appropriate management with regard to anti-coagulation. Further studies on the outcomes of these patients are warranted.

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.

Myocardial infarction after left ventricular assist device implantation: clinical course, role of aortic root thrombus, and outcomes.

1. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-56. 2. Topilsky Y, Maltais S, Oh JK, et al. Focused review on transthoracic echocardiographic assessment of patients with continuous axial left ventricular assist devices. Cardiol Res Pract 2011; Feb 8 Epub. http://www. hindawi.com/journals/crp/2011/187434/. Accessed August 6, 2013. 3. Uriel N, Morrison KA, Garan AR, et al. Development of a novel echocardiography ramp test for speed optimization and diagnosis of device thrombosis in continuous-flow left ventricular assist devices: the Columbia ramp study. J Am Coll Cardiol 2012;60:1764-75. 4. Pak SW, Uriel N, Takayama H, et al. Prevalence of de novo aortic insufficiency during long-term support with left ventricular assist devices. J Heart Lung Transplant 2010;29:1172-6.

Correlation Between Home INR and Core Laboratory INR in Patients Supported with Continuous-Flow Left Ventricular Assist Devices.

It has been well established that patient self-testing (PST) of international normalized ratio (INR) using home monitoring devices increases the average therapeutic time and patient satisfaction. Long-term anticoagulation therapy with warfarin is used in patients with continuous-flow left ventricular assist device (CF-LVAD) to minimize the occurrence of thromboembolic events; however, PST devices have never been tested in patients with CF-LVADs. The purpose of this study was to determine the reliability of the PST device Alere INRatio 2 in patients supported with CF-LVADs. A correlation study was performed in 50 patients with CF-LVAD who were on stable warfarin therapy for a minimum of 3 weeks. Simultaneous INR values were determined from capillary whole blood samples using the Alere PST device and venous blood samples processed in the core laboratory at Columbia University Medical Center. There was a moderate correlation between the venous and the capillary INR values with a correlation coefficient of 0.83. The median difference between the methods was 0.39, with 44 of 50 patients recording higher INRs with Alere. Results remained unchanged after adjusting for use of amiodarone, abnormal hematocrit and liver enzymes, creatinine, and thyroid-stimulating hormone. Point of care testing with Alere correlates moderately well but consistently overestimates INR when compared with conventional laboratory testing in patients with CF-LVAD.

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.

Clinical and hemodynamic effects of intra-aortic balloon pump therapy in chronic heart failure patients with cardiogenic shock

BACKGROUND The role of the intra-aortic balloon pump (IABP) in acute decompensated heart failure (HF) with cardiogenic shock (CS) is largely undefined. In this study we sought to assess the hemodynamic and clinical response to IABP in chronic HF patients with CS and identify predictors of response to this device. METHODS We retrospectively reviewed all patients undergoing IABP implantation from 2011 to 2016 at our institution to identify chronic HF patients with acute decompensation and CS (cardiac index <2.2 liters/min/m2 and systolic blood pressure <90 mm Hg or need for vasoactive medications to maintain this level). Clinical deterioration on IABP was defined as failure to bridge to either discharge on medical therapy or durable heart replacement therapy (HRT; durable left ventricular assist device or heart transplant) with IABP alone. RESULTS We identified 132 chronic HF patients with IABP placed after decompensation with hemodynamic evidence of CS. Overall 30-day survival was 84.1%, and 78.0% of patients were successfully bridged to HRT or discharge without need for escalation of device support. The complication rate during IABP support was 2.3%. Multivariable analysis identified ischemic cardiomyopathy (odds ratio [OR] 3.24, 95% confidence interval [CI] 1.16 to 9.06; p = 0.03) and pulmonary artery pulsatility index (PAPi) <2.0 (OR 5.04, 95% CI 1.86 to 13.63; p = 0.001) as predictors of clinical deterioration on IABP. CONCLUSIONS Overall outcomes with IABP in acute decompensated chronic HF patients are encouraging, and IABP is a reasonable first-line device for chronic HF patients with CS. Baseline right ventricular function, as measured by PAPi, is a major predictor of outcomes with IABP in this population.