Elevated resting heart rate in heart transplant recipients: innocent bystander or adverse prognostic indicator?

BACKGROUND: The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality. METHODS: The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared. RESULTS: Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively. CONCLUSION: Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation.

Impact of high-dose inotropic donor support on early myocardial necrosis and outcomes in cardiac transplantation.

BACKGROUND: Cardiac donors routinely require vasoactive agents for circulatory stability after brain death. Nevertheless, inotropes have been associated with direct cardiac toxicity. Our study evaluated whether the use of high-dose inotropic support in potential donors was associated with increased early myocardial necrosis (MN) and worse clinical outcomes after cardiac transplantation. METHODS: The UTAH Cardiac Transplant Program (UCTP) and Intermountain Donor Services databases were queried for records between 1996 and 2009. The high-dose donor inotropic support (HDIS) group was defined as patients on dopamine >10 µg/kg/min. The incidence of early MN, intensive care unit (ICU) length of stay, length of ventilator support, and mortality was evaluated. RESULTS: Two hundred and forty-four recipients undergoing transplant met study criteria. The average donor age was 27 yr. The incidence of MN in the HDIS (n=29) and non-HDIS (n=204) groups was 14.8% and 6.7%, respectively, OR 2.67. Total ischemic time, ventilator support time, ICU stay, and actuarial survival were similar between both groups. CONCLUSION: The use of high-dose inotropic support to maintain donor stability appears to have a higher trend for early post-transplant MN without an impact on clinical outcomes. With the current growing shortage of organ donors, it appears reasonable to use donors on high-dose inotropic support.

Management of unstable arrhythmias in cardiogenic shock.

OPINION STATEMENT: Atrial and ventricular arrhythmias commonly arise in the setting of cardiogenic shock and often result in hemodynamic deterioration. Causative factors include myocardial ischemia, volume overload, and metabolic disturbances. Correcting these factors plays an important role in managing arrhythmias in this setting. Ventricular arrhythmias are more ominous compared to atrial arrhythmias but both require prompt intervention with electrical shock and anti-arrhythmic drug suppression. Coronary reperfusion is key to improving survival, including reducing the risk of sudden cardiac arrest, in acute myocardial infarction. Case series have also demonstrated the value of intra-aortic balloon pump counter-pulsation in suppressing ventricular arrhythmias in cardiogenic shock. The mechanism of arrhythmia suppression may be due to improved coronary perfusion and afterload reduction. Percutaneous ventricular assist device placement may be effective in this setting; however, data addressing this specific endpoint are lacking. Anti-arrhythmic drug options for ventricular and atrial arrhythmia suppression, in the setting of cardiogenic shock, are relatively limited. Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone. The other Class III agents, sotalol and dronedarone, are excluded due to associated mortality observed in the SWORD and ANDROMEDA trials, respectively. Dofetilide is renally excreted and causes QT interval prolongation. Care should be taken to avoid excessive drug accumulation due to poor kidney perfusion and function. Dofetilide is approved for use for atrial arrhythmias and has not been studied for ventricular arrhythmia suppression. The DIAMOND-CHF trial established its safety in the setting of heart failure. Amiodarone is very effective in suppressing both atrial and ventricular arrhythmias. It is often the drug of choice in heart failure. Its off-label use for atrial arrhythmias is very common. Care should be taken with intravenous amiodarone to avoid hypotension.

Favorable Effects on Pulmonary Vascular Hemodynamics with Continuous-Flow Left Ventricular Assist Devices Are Sustained 5 Years After Heart Transplantation.

It is unclear whether pulmonary hemodynamics improvement with left ventricle unloading with left ventricular assist devices (LVADs) is sustained long term after heart transplant (HT). We sought to assess the effects on pulmonary vascular hemodynamics during continuous-flow (CF-LVAD) and pulsatile flow (PF-LVAD) support up to 5 years after HT. Invasive hemodynamics were evaluated before LVAD, before HT, and at 3 months, 1, and 3-5 years posttransplant. Thirty-eight patients were included in the study and divided into two groups according to the type of LVAD support. The two groups were well matched in age and gender. Mean pulmonary artery pressure (PAPm) and systolic PAP (PAPs) improved significantly in the PF-LVAD group (40 ± 10.6 to 19.8 ± 4.4 mm Hg and 62.7 ± 14.9 to 31.8 ± 5.9 mm Hg, respectively) and in the CF-LVAD group (37.4 ± 11.6 to 22.4 ± 7.7 mm Hg and 53.7 ± 18.0 to 34.6 ± 11.8 mm Hg, respectively). Reductions in PAPm and PAPs were more pronounced in PF-LVAD group than in CF-LVAD group (p = 0.005 and p = 0.03, respectively). After HT, the improvement in PAPm and PAPs was sustained after 3-5 years in patients who received PF-LVAD (22.6 ± 6.5 and 32.2 ± 9.2 mm Hg, respectively) and in patients who received CF-LVAD (22.2 ± 8.4 and 33.8 ± 9.6 mm Hg, respectively). In conclusion, long-term LVAD support resulted in significant improvement in PAPm and PAPs regardless of the pump generation. The improvement in hemodynamics observed during LVAD support was sustained 3-5 years posttransplant.

Managing Stenotic Septal Perforator Branches.

Coronary artery disease of the septal perforator branches can lead to clinical ischemia and conduction abnormalities. Performing interventional procedures in these vessels is frequently impossible because they are small, which makes it difficult to approach them and to select appropriate equipment. Larger septal perforator branches have been treated percutaneously in a few patients; however, the clinical effectiveness and long-term outcomes are not known. We present our experience in managing obstructive septal perforator branch stenosis in 4 patients.

Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery.

OBJECTIVES: This study sought to prospectively investigate the longitudinal effects of continuous-flow left ventricular assist device (LVAD) unloading on myocardial structure and systolic and diastolic function. BACKGROUND: The magnitude, timeline, and sustainability of changes induced by continuous-flow LVAD on the structure and function of the failing human heart are unknown. METHODS: Eighty consecutive patients with clinical characteristics consistent with chronic heart failure requiring implantation of a continuous-flow LVAD were prospectively enrolled. Serial echocardiograms (at 1, 2, 3, 4, 6, 9, and 12 months) and right heart catheterizations were performed after LVAD implant. Cardiac recovery was assessed on the basis of improvement in systolic and diastolic function indices on echocardiography that were sustained during LVAD turn-down studies. RESULTS: After 6 months of LVAD unloading, 34% of patients had a relative LV ejection fraction increase above 50% and 19% of patients, both ischemic and nonischemic, achieved an LV ejection fraction ≥ 40%. LV systolic function improved as early as 30 days, the greatest degree of improvement was achieved by 6 months of mechanical unloading and persisted over the 1-year follow up. LV diastolic function parameters also improved as early as 30 days after LVAD unloading, and this improvement persisted over time. LV end-diastolic and end-systolic volumes decreased as early as 30 days after LVAD unloading (113 vs. 77 ml/m(2), p < 0.01, and 92 vs. 60 ml/m(2), p < 0.01, respectively). LV mass decreased as early as 30 days after LVAD unloading (114 vs. 95 g/m(2), p < 0.05) and continued to do so over the 1-year follow-up but did not reach values below the normal reference range, suggesting no atrophic remodeling after prolonged LVAD unloading. CONCLUSIONS: Continuous-flow LVAD unloading induced in a subset of patients, both ischemic and nonischemic, early improvement in myocardial structure and systolic and diastolic function that was largely completed within 6 months, with no evidence of subsequent regression.

Pulsatility and the risk of nonsurgical bleeding in patients supported with the continuous-flow left ventricular assist device HeartMate II.

BACKGROUND: Bleeding is an important cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (LVADs). Reduced pulsatility has been implicated as a contributing cause. The aim of this study was to assess the effects of different degrees of pulsatility on the incidence of nonsurgical bleeding. METHODS AND RESULTS: The Utah Transplantation Affiliated Hospitals (U.T.A.H.) heart failure and transplant program databases were queried for patients with end-stage heart failure who required support with the continuous-flow LVAD HeartMate II (Thoratec Corp, Pleasanton, CA) between 2004 and 2012. Pulsatility was evaluated by means of the LVAD parameter pulsatility index (PI) and by the echocardiographic assessment of aortic valve opening during the first 3 months of LVAD support. PI was analyzed as a continuous variable and also stratified according to tertiles of all the PI measurements during the study period (low PI: <4.6, intermediate PI: 4.6-5.2, and high PI: >5.2). Major nonsurgical bleeding associated with a decrease in hemoglobin ≥2 g/dL (in the absence of hemolysis) was the primary end point. A total of 134 patients (median age of 60 [interquartile range: 49-68] years, 78% men) were included. Major bleeding occurred in 33 (25%) patients (70% gastrointestinal, 21% epistaxis, 3% genitourinary, and 6% intracranial). In multivariable analysis, PI examined either as a categorical variable, low versus high PI (hazard ratio, 4.06; 95% confidence interval, 1.35-12.21; P=0.04), or as a continuous variable (hazard ratio, 0.60; 95% confidence interval, 0.40-0.92; P=0.02) was associated with an increased risk of bleeding. CONCLUSIONS: Reduced pulsatility in patients supported with the continuous-flow LVAD HeartMate II is associated with an increased risk of nonsurgical bleeding, as evaluated by PI.

Management of chemotherapy induced cardiomyopathy.

Chemotherapy related cardiac dysfunction (CRCD) is a serious complication of anticancer therapy. CRCD can be classified into two types. Type I CRCD is exemplified by anthracyline- induced cardiac dysfunction and type II CRCD is exemplified by trastuzumab- induced cardiac dysfunction. The mechanism of cardiac toxicity in both types is not well defined. Certain risk factors may play a role in developing the cardiac injury, most importantly, the cumulative dose when dealing with anthracycline induced cardiotoxicity. Establishing an early diagnosis and initiating early treatment may be an important step in preventing irreversible cardiac injury especially in type I CRCD. Currently there are no guidelines developed specifically for the treatment of chemotherapy induced cardiomyopathy (CIC), however a few small studies support the use of neurohormonal antagonists in the treatment and prevention of CIC. Large multi- centers trials are needed to establish guidelines for CIC. Until then, we advocate following the American College of Cardiology/ American Heart Association (ACC/AHA) and Heart Failure Society of America (HFSA) guidelines. Additionally, a close collaboration between the patient's cardiologist and oncologist is strongly recommended in order to establish a long term plan for the patient.

Saw palmetto-induced pancreatitis.

Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.