George Sokos

Safe Use of Hemodialysis for Dabigatran Removal before Cardiac Surgery

OBJECTIVE: To describe a case in which hemodialysis was performed before cardiac transplantation in an attempt to reverse the effects of dabigatran and reduce the risk of bleeding associated with surgery. CASE SUMMARY: A 59-year-old female with heart failure and atrial fibrillation was admitted for orthotropic heart transplant. She had been stable at home with continuous milrinone therapy 0.25 μg/kg/min, amiodarone 200 mg twice daily, and dabigatran 150 mg twice daily for stroke prevention secondary to atrial fibrillation. Upon notification of organ availability, the patient was admitted to the hospital for transplant surgery, with her last dose of dabigatran taken approximately 36 hours before admission. Coagulation studies indicated normal activated partial thromboplastin time, slightly elevated international normalized ratio of 1.2, and elevated thrombin time (TT) of 90.6 seconds (upper limit of normal 19.9 seconds). A hemodialysis catheter was emergently placed and dialysis was initiated. One hour after initiation, TT decreased to 65.5 seconds. After 2.5 hours of dialysis, TT further decreased to 60.2 seconds; at that time, the patient underwent transplantation with no abnormal bleeding during or following surgery. DISCUSSION: Minimal data exist on techniques to reverse the effects of dabigatran in cases of bleeding or emergent surgery. This case examines the efficacy of hemodialysis to decrease dabigatrans effect on clotting assays prior to surgery to reduce the risk of bleeding. In this case, a TT of 60.2 seconds with recent dabigatran administration did not result in abnormal bleeding associated with cardiac surgery. CONCLUSIONS: To our knowledge, this case report represents the first published data on the effects of hemodialysis on dabigatran removal and reversal of anticoagulation associated with dabigatran before surgery. The routine use of preoperative hemodialysis in patients on dabigatran is not recommended; however, the potential efficacy in such circumstances is supported by the successful results in this case.

Usefulness of Isosorbide Dinitrate and Hydralazine as Add-on Therapy in Patients Discharged for Advanced Decompensated Heart Failure

Data supporting the use of oral isosorbide dinitrate and/or hydralazine (I/H) as add-on therapy to standard neurohormonal antagonists in advanced decompensated heart failure (ADHF) are limited, especially in the non-African-American population. Our objective was to determine if addition of I/H to standard neurohormonal blockade in patients discharged from the hospital with ADHF is associated with improved hemodynamic profiles and improved clinical outcomes. We reviewed consecutive patients with ADHF admitted from 2003 to 2006 with a cardiac index < or =2.2 L/min/m(2) admitted for intensive medical therapy. Patients discharged with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (control group) were compared with those receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers plus I/H (I/H group). The control (n = 97) and I/H (n = 142) groups had similar demographic characteristics, baseline blood pressure, and renal function. Patients in the I/H group had a significantly higher estimated systemic vascular resistance (1,660 vs 1,452 dynes/cm(5), p <0.001) and a lower cardiac index (1.7 vs 1.9 L/min/m(2), p <0.001) on admission. The I/H group achieved a similar decrease in intracardiac filling pressures and discharge blood pressures as controls, but had greater improvement in cardiac index and systemic vascular resistance. Use of I/H was associated with a lower rate of all-cause mortality (34% vs 41%, odds ratio 0.65, 95% confidence interval 0.43 to 0.99, p = 0.04) and all-cause mortality/heart failure rehospitalization (70% vs 85%, odds ratio 0.72, 95% confidence interval 0.54 to 0.97, p = 0.03), irrespective of race. In conclusion, the addition of I/H to neurohormonal blockade is associated with a more favorable hemodynamic profile and long-term clinical outcomes in patients discharged with low-output ADHF regardless of race.

Antigenic stimulation in the simian model of HIV infection yields dilated cardiomyopathy through effects of TNFα

Objective:To investigate a role for endogenous myocardial cytokine production in the development of HIV-associated cardiomyopathy. Design:Cardiomyopathy is a late-stage sequela of HIV infection. Although pathogenesis of this condition in HIV infection is poorly defined, inflammatory cytokines are recognized for their detrimental effects on myocardial structure and function. HIV infection is characterized by chronic immune activation and inflammatory cytokine dysregulation. As the myocardium itself is a rich potential source of inflammatory cytokines, HIV-mediated cytokine dysregulation may be an important contributor to development of HIV cardiomyopathy. An antigenic stimulation protocol conducted in the simian immunodeficiency virus (SIV) model of HIV infection was used to study the effects of endogenous cytokine production on myocardial structure and function. Methods:Twenty-six rhesus monkeys were assigned to treatment groups for a 35-day study. Animals were SIV-infected; SIV-infected and treated with killed Mycobacterium avium complex bacteria (MAC); SIV-infected, MAC-treated, and given the TNFα antagonist etanercept; or uninfected and MAC-treated. All animals were subjected to weekly echocardiographic studies. Hearts were collected for further evaluation at euthanasia. Results:SIV-infected, MAC-treated animals developed significant systolic dysfunction [left ventricular ejection fraction (LVEF) decline of 19 ± 2%] and ventricular chamber dilatation [left ventricular end-diastolic diameter (LVEDD) increase of 26 ± 6%] not seen in other groups. Concurrent treatment with etanercept prevented development of these changes, implicating a causative role of myocardial TNFα. Conclusions:SIV-infected animals develop exaggerated myocardial pathology on stimulation with the ubiquitous environmental agent MAC. These responses are TNFα-dependent and may play a significant role in the development of cardiomyopathy in HIV infection.

Role of Phosphodiesterase-5 Inhibitors in Heart Failure: Emerging Data and Concepts

Novel treatment of congestive heart failure (HF) involves utilizing unique pathways to improve upon contemporary therapies. Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Preclinical studies suggest a favorable myocardial effect of PDE5 inhibitors by blocking adrenergic, hypertrophic and pro-apoptotic signaling, thereby supporting their use in HF. The clinical benefits of acute and chronic PDE5 inhibition on lung diffusion capacity, exercise performance and ejection fraction in humans are emerging and appear promising. Larger, controlled trials are now on-going to assess the safety, efficacy and tolerability of PDE5 inhibitors on morbidity and mortality in patients with both systolic and diastolic heart failure. If the results of these trials are positive, a new avenue for the treatment of HF will open, which will help curtail the societal effects of this costly and morbid disease.

Salvage Peripheral Extracorporeal Membrane Oxygenation Using Cobe Revolution® Centrifugal Pump as a Bridge to Decision for Acute Refractory Cardiogenic Shock

Abstract  Objectives: Acute refractory cardiogenic shock with early multisystem organ failure has a poor outcome without mechanical circulatory support. We review our experience with emergent peripheral cardiopulmonary support as a bridge to decision in these patients. Methods: A retrospective review from January 2009 through December 2010 was conducted of 26 consecutive adult patients at a single institution with acute refractory cardiogenic shock who underwent salvage peripheral cardiopulmonary support. Results: There were 18 men and 8 women with a mean age of 54 years (range 18 to 76). Indications for support: acute myocardial infarction (n = 16), decompensated chronic heart failure (n = 2), refractory arrhythmic arrest (n = 3), acute valvular pathology (n = 4), and unknown (n = 1). Patients with primary postcardiotomy shock were excluded. Median duration of support was 3 days (range 1 to 14). Decisions included: withdraw of support (n = 4), recovery (n = 5), and bridge to a procedure (n = 17). The procedures were percutaneous coronary intervention (n = 4), left ventricular assist device (n = 9), heart transplantation (n = 1), and miscellaneous cardiac surgery (n = 3). Overall survival to discharge was 65%. In the recovery and bridge to a procedure group, 78% were discharged from the hospital and survival at three months was 72%. Conclusions: Salvage peripheral cardiopulmonary support is a useful tool to rapidly stabilize acute refractory cardiogenic shock permitting an assessment of neurologic and end‐organ viability. (J Card Surg 2012;27:521‐527)

Worsening Heart Failure in the Setting of Dronedarone Initiation

Objective: To describe a challenging patient case in which dronedarone was selected for a patient with atrial fibrillation and heart failure; the drug may have been associated with worsening heart failure, leading to acute renal and hepatic failure. Case Summary: A 47-year-old male with a history of heart failure with New York Heart Association class III—IV symptoms presented to our institution with ventricular fibrillation and ventricular tachycardia storm. Torsade de pointes secondary to a combination of doletilide and hypokalemia was determined to be the etiology. Upon stabilization, the patient was initiated on dronedarone 400 mg orally twice daily by the electro physiology service for atrial fibrillation. The patient had a questionable history of amkxtaroπe intolerance. By hospital day 9 (day 4 of dronedarone therapy), the patient demonstrated a clinical picture consistent with acute renal and hepatic failure possibly due to worsening heart failure. Dronedarone was discontinued on hospital day 10. He was subsequently transferred to an outside hospital where he required milrinone therapy for cardiogenic shock. Laboratory markers of renal and hepatic function improved over the remainder of his hospitalization and he was discharged on hospital day 20. Discussion: Dronedarone is a newly approved antiarrhythmic agent with multichannel blocking properties similar to amiodarone. Use of the Naranjo probability scale determined that this patients worsening heart failure leading to acute renal and hepatic failure was possibly caused by dronedarone. The implication from the ANDROMEDA trial as well as our experience in this case is that dronedarone should be used cautiously in patients with heart failure and avoided in patients specifically outlined in the product labeling. Conclusions: This case report, to our knowledge, represents the first published postmarketing report of worsening heart failure complicated by multiorgan dysfunction in the setting of dronedarone initiation. Dronedarone use must be approached with caution in patients with a history of heart failure.

Sexual function after left ventricular assist device.

To the Editor: Impaired sexual function is common in patients with heart failure ([1][1]) and following cardiac transplant. Left ventricular assist devices (LVADs) improve survival, functional capacity, and quality of life for end-stage heart failure, but data regarding their impact on sexual

Transitioning from parenteral treprostinil to inhaled treprostinil in patients with pulmonary arterial hypertension.

Treprostinil is a potent prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH, World Health Organization Group I). Previously, treprostinil was available only in subcutaneous (SC) or intravenous (IV) formulations. Availability of an inhaled formulation of treprostinil has provided clinicians with an alternative to continuous SC or IV treprostinil in appropriate patients. Stable PAH patients whose quality of life has been dramatically impacted by side effects of parenteral therapy or those who have had recurrent, life-threatening bloodstream infections but are otherwise responding well to treatment may be the candidates for continuing prostacyclin therapy with inhaled treprostinil. However, there is little clinical experience with transitioning patients from parenteral to inhaled treprostinil. We present the results of two cases that highlight important considerations in transitioning patients from parenteral to inhaled therapy, including the pharmacologic and clinical equivalence of formulations, dose titration of formulations and suggested criteria for patient selection.

Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis for LVAD and transplantation risk in patients with newly diagnosed dilated cardiomyopathy—preliminary observations from a high-volume transplant centre

Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high‐risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration.BACKGROUND Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high-risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration. METHODS Over 49 consecutive months, 61 consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ). Inclusion criteria for a primary non-ischaemic DCM and EF <45% were met in 31 patients. DCM patients were categorized into: (i) presence of midwall LV stripe (+Stripe) and (ii) absence of midwall stripe (-Stripe) groups. Primary outcome was defined by the composite of death, need for LV assist device (LVAD), and urgent orthotopic cardiac transplantation (Tx) during a 12-month follow-up period. Kaplan-Meier survival analysis was conducted grouping patients by +Stripe and -Stripe. RESULTS There were no differences between groups for demographics, blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There were 18 patients (58%) with +Stripe. Nine events occurred: seven patients required urgent Tx and/or LVAD implantation and two patients died. The +Stripe categorization strongly predicted the need for LVAD, urgent Tx surgery, and death (log-rank = 9, P = 0.002). All the events occurred in the +Stripe patients with no MACE experienced in the -Stripe group. The -Stripe group experienced marked signs of improvement in LVEF (P = 0.01) at follow-up. LVEDD was predictive of need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter predicted MACE. CONCLUSIONS The presence of +Stripe on CMR is strongly predictive of LVAD, transplant need, and death during a 12-month follow-up period in DCM patients in this proof of concept study. All -Stripe patients survived without experiencing any events. Incorporating CMR imaging into routine clinical practice may have prognostic value in DCM patients; indicating conservative management in low-risk patients while expectantly managing high-risk patients.

Management of pulmonary hypertension due to heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a major cause of HF-related morbidity and mortality, with no medical therapy proven to modify the underlying disease process and result in improvements in survival. With long-standing pulmonary venous congestion, a majority of HFpEF patients develop pulmonary hypertension (PH). Elevated pulmonary pressures have been shown to be a major determinant of mortality in this population. Given the paucity of available disease-modifying therapies for HFpEF, there has been a considerable interest in evaluating new therapeutic options specifically targeting PH in this patient population.