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Background In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus maximally tolerated guideline-directed medical therapy (GDMT) improved clinical outcomes compared with GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to left ventricular (LV) dysfunction. Aims In this COAPT substudy, we sought to evaluate two-year outcomes in HF patients with reduced LV ejection fraction (HFrEF; LVEF ≤40%) versus preserved LVEF (HFpEF; LVEF >40%) and in those with severe (LVEF ≤30%) versus moderate (LVEF >30%) LV dysfunction. Methods The principal effectiveness outcome was the two-year rate of death from any cause or HF hospitalisations (HFH). Subgroup analysis with interaction testing was performed according to baseline LVEF; 472 patients (82.1%) had HFrEF (mean LVEF 28.0%±6.2%; range 12% to 40%) and 103 (17.9%) had HFpEF (mean LVEF 46.6%±4.9%; range 41% to 65%), while 292 (50.7%) had severely depressed LVEF (LVEF ≤30%; mean LVEF 23.9%±3.8%) and 283 (49.3%) had moderately depressed LVEF (LVEF >30%; mean LVEF 39.0%±6.8%). Results The two-year rate of death or HFH was 56.7% in patients with HFrEF and 53.4% with HFpEF (HR 1.16, 95% CI: 0.86-1.57, p=0.32). MitraClip reduced the two-year rate of death or HFH in patients with HFrEF (HR 0.50, 95% CI: 0.39-0.65) and HFpEF (HR 0.60, 95% CI: 0.35-1.05), pint=0.55. MitraClip was consistently effective in reducing the individual endpoints of mortality and HFH, improving MR severity, quality of life, and six-minute walk distance in patients with HFrEF, HFpEF, LVEF ≤30%, and LVEF >30%. Conclusions In the COAPT trial, among patients with HF and 3+ or 4+ SMR who remained symptomatic despite maximally tolerated GDMT, the MitraClip was consistently effective in improving survival and health status in patients with severe and moderate LV dysfunction and those with preserved LVEF.

Targeted blood pressure (BP) control is a goal of left ventricular assist device medical management, but the interpretation of values obtained from noninvasive instruments is challenging. In the MOMENTUM 3 Continued Access Protocol, paired BP values in HeartMate 3 (HM3) patients were compared from arterial (A)-line and Doppler opening pressure (DOP) (319 readings in 261 patients) and A-line and automated cuff (281 readings in 247 patients). Pearson (R) correlations between A-line mean arterial (MAP) and systolic blood pressures (SBP) were compared with DOP and cuff measures according to the presence (>1 pulse in 5 seconds) or absence of a palpable radial pulse. There were only moderate correlations between A-line and noninvasive measurements of SBP (DOP R = 0.58; cuff R = 0.47) and MAP (DOP R = 0.48; cuff R = 0.37). DOP accuracy for MAP estimation, defined as the % of readings within ± 10 mmHg of A-line MAP, decreased from 80% to 33% for DOP ≤ 90 vs. >90 mmHg, and precision also diminished (mean absolute difference [MAD] increased from 6.3 ± 5.6 to 16.1 ± 11.4 mmHg). Across pulse pressures, cuff MAPs were within ±10 mmHg of A-line 62.9%-68.8% of measures and MADs were negligible. The presence of a palpable pulse reduced the accuracy and precision of the DOP-MAP estimation but did not impact cuff-MAP accuracy or precision. In summary, DOP may overestimate MAP in some patients on HM3 support. Simultaneous use of DOP and automated cuff and radial pulse may be needed to guide antihypertensive medication titration in outpatients on HM3 support.

In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079).

Continuous-flow left ventricular assist devices are frequently used for management of patients with advanced heart failure with reduced ejection fraction. Although technologic advancements have contributed to improved outcomes, several complications arise over time. These complications result from several factors, including medication effects, physiologic responses to chronic exposure to circulatory support that is minimally/entirely nonpulsatile, and dysfunction of the device itself. Clinical presentation can range from chronic and indolent to acute, life-threatening emergencies. Several areas of uncertainty exist regarding best practices for managing complications; however, growing awareness has led to development of new guidelines to reduce risk and improve outcomes.

Background: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. Methods: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. Results: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P =0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P Conclusions: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01626079.

Objectives This study sought to assess the sex-specific outcomes in patients with heart failure (HF) with 3+ and 4+ secondary mitral regurgitation (SMR) treated with transcatheter mitral valve repair (TMVr) plus guideline-directed medical therapy (GDMT) versus GDMT alone in the COAPT trial. Background The impact of sex in patients with HF and severe SMR treated with TMVr with the MitraClip compared with GDMT alone is unknown. Methods Patients were randomized 1:1 to TMVr versus GDMT alone. Two-year outcomes were examined according to sex. Results Among 614 patients, 221 (36.0%) were women. Women were younger than men and had fewer comorbidities, but reduced quality of life and functional capacity at baseline. In a joint frailty model accounting for the competing risk of death, the 2-year cumulative incidence of the primary endpoint of all HF hospitalizations (HFH) was higher in men compared with women treated with GDMT alone. However, the relative reduction in HFHs with TMVr was greater in men (HR: 0.43; 95% CI: 0.34-0.54) than women (HR: 0.78; 95% CI: 0.57-1.05) (Pinteraction = 0.002). A significant interaction between TMVr versus GDMT alone treatment and time was present for all HFHs in women (HR: 0.57; 95% CI: 0.39-0.84, and HR: 1.39; 95% CI: 0.83-2.33 between 0-1 year and 1-2 years after randomization, respectively, Pinteraction = 0.007) but not in men (HR: 0.48; 95% CI: 0.36-0.64, and HR: 0.33; 95% CI: 0.21-0.51; Pinteraction = 0.16). Female sex was independently associated with a lower adjusted risk of death at 2 years (HR: 0.64; 95% CI: 0.46-0.90; P = 0.011). TMVr consistently reduced 2-year mortality compared with GDMT alone, irrespective of sex (Pinteraction = 0.99). Conclusions In the COAPT trial, TMVr with the MitraClip resulted in improved clinical outcomes compared with GDMT alone, irrespective of sex. However, the impact of TMVr in reducing HFH was less pronounced in women compared with men beyond the first year after treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Tria] [COAPT]; NCT01626079 )

The aim of this study was to measure aortic vascular stiffness from orthotopic heart transplant (OHT) patients exposed to varying types of flow as a result of the presence or absence of left ventricular assist device (LVAD) support pre-OHT.The effects of continuous-flow LVADs (CF-LVADs) on vascular properties are unknown, but may contribute to the pathophysiology of CF-LVAD complications such as stroke, hypertension, and bleeding.Echocardiograms were reviewed from 172 OHT patients immediately before LVAD and at 3 time points post-OHT: baseline, 6 months, and 1 year. For each study, pulse pressure and aortic end-systolic and end-diastolic dimensions were used to calculate aortic strain, distensibility, and stiffness index. Patients were categorized into 3 groups based on the presence or absence of a LVAD and a pulse pre-OHT: No LVAD (n = 111), LVAD No Pulse (n = 30), and LVAD With Pulse (n = 31).The aortic stiffness index among LVAD No Pulse patients increased from 2.8 ± 1.1 pre-CF-LVAD to 10.9 ± 4.7 immediately post-OHT (p 0.001). This aortic stiffness index was also significantly higher compared with No LVAD (3.4 ± 1.1; p 0.001) and LVAD With Pulse (3.7 ± 1.4; p 0.001) immediately post-OHT with attenuation of these differences by 1 year post-OHT. Similar findings were noted for the other indices of aortic stiffness.Aortic stiffness is markedly increased immediately post-OHT among patients bridged with CF-LVADs, with attenuation of this increased stiffness over the first year after transplant. These results suggest that aortic vascular properties are dynamic and may be influenced by alterations in flow pulsatility. As more patients are supported with CF-LVADs and as newer pump technology attempts to modulate pulsatility, further research examining the role of alterations in flow patterns on vascular function and the potential resultant systemic sequelae are needed.

Purpose Targeted blood pressure (BP) control is a goal of LVAD medical management, but the interpretation of values obtained from automated cuffs and Doppler opening pressure (DOP) is challenging. The aim herein is to compare BP values obtained using arterial line (A-Line) and noninvasive measures in patients on HeartMate 3 support. Methods In the MOMENTUM 3 Continued Access Protocol, paired BP values from A-Line and DOP (354 readings in 277 patients) and A-Line and automated cuff (296 readings in 256 patients) were obtained (>90% ≤7 days postop). Pearson (R) correlations between A-Line and cuff systolic blood pressure (SBP), mean arterial pressure (MAP), and DOP were assessed. A-Line and noninvasive BP measurements in the absence or presence of a palpable radial pulse (>1 in 5 seconds) were also compared. Results There were moderate correlations between A-Line SBP and DOP (R=0.63) and A-Line MAP and DOP (R=0.53) (Fig. A, B). DOP was 4±10 mmHg higher than A-Line MAP and 8±11 mmHg lower than A-Line SBP. When DOP was ≤90 mmHg, the mean absolute difference between DOP and A-Line MAP was 6 ± 6 mmHg compared to 10 ± 9 mmHg between DOP and A-Line SBP. At higher pressures, the disparity between DOP and A-Line MAP increased. The presence of a palpable pulse and high pulse pressure reduced DOP accuracy (Fig. C, D). With a palpable pulse, only 64% DOP values were within 10 mmHg of the A-Line MAP. The correlations between cuff SBP to A-line SBP and cuff MAP to A-Line MAP were poor (Fig. E, F, R=0.36-0.45), but the presence of a palpable pulse and high pulse pressure improved cuff accuracy (Fig. G,H). With a palpable pulse, 71% of cuff MAP values were within 10 mmHg of A-Line. Conclusion On average, DOP is lower than A-Line SBP and higher than A-Line MAP. In patients with DOP ≤90 mmHg or without a radial pulse, it may be reasonable to interpret DOP as the MAP. The presence of a palpable pulse or high pulse pressure reduces DOP accuracy but improves cuff MAP accuracy. When DOP is >90 mmHg, DOP should not be interpreted as MAP; cuff measures may yield greater accuracy.

Survival of children born with congenital heart disease (CHD) has been improving for decades, thanks to improvements in surgical techniques and postoperative care. Adults with congenital heart disease (ACHD) now outnumber children with CHD. As survival into adulthood has increased, so has the complexity and severity of CHD in addition to the association of heart failure (HF) in ACHD. ACHD HF is unique compared to non-ACHD HF in adults, and its evaluation and management were outlined in a statement by the American Heart Association. ACHD HF is less likely to be primarily ischemic. There are heterogeneous anatomic lesions. Many have failing systemic right ventricles (RV) that are not designed to pump against systemic resistance. Additionally, anemia, cyanosis, HF multiplied across decades, chronotropic incompetence, and a higher risk of arrhythmias complicate the disease course. There is lack of evidence-based data to guide medical treatments, interventions, and surgical therapies. This chapter reviews management of adult patients with CGD who require individualization based on the patient’s anatomy, physiology, and comorbidities.

The impact of sex on clinical outcomes in patients with heart failure and moderate-severe or severe secondary mitral regurgitation treated with transcatheter mitral valve repair with MitraClip + guideline-directed medical therapy (device) versus guideline-directed medical therapy alone (control) is

In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus guideline directed medical therapy (GDMT) improved 2-year clinical outcomes in comparison to GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to LV

In the COAPT trial, transcatheter mitral valve repair with the MitraClip plus guideline directed medical therapy (GDMT) improved clinical outcomes in comparison to GDMT alone in symptomatic patients with heart failure (HF) and 3+ or 4+ secondary mitral regurgitation (SMR) due to LV dysfunction. We

Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%.Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P0.001).Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079 .).

Background Patients with severe mitral regurgitation (MR) and cardiogenic shock are typically too high risk for immediate surgery; however, percutaneous edge-to-edge mitral valve repair (pMVr) may be reasonable in select patients. Aim Describe characteristics and outcomes of patients who underwent pMVr with and without shock at a single center. Methods Chart review of all patients who underwent non-investigational pMVr from November 2013 to October 2018. Shock was defined as dependence on an intravenous (IV) inotrope, IV afterload reduction, and/or temporary mechanical circulatory support immediately preceding pMVr. Results There were 135 patients. Mean age was 80 ± 12 years and 56 (41%) were female. Twelve (8.9%) had shock. All patients had 3+ or 4+ MR at baseline. Post-procedure, all shock patients had 2+ or less MR. Two (17%) shock patients and 4 (3%) non-shock patients died within 30 days of pMVr (P = 0.03). Six (50%) shock patients had resolution of shock and discharged home (primary outcome). Five shock patients had acute MI, four of whom met the primary outcome. Four shock patients had chronic MR (>21 days), three of whom did not meet the primary outcome. Overall, follow-up time for mortality was median (IQR) 198 (42-379) days. Shock patients who survived to 30 days post-procedure had significantly shorter time from diagnosis of MR to pMVr compared to those who died (35 ± 68 vs. 374 ± 111 days; P = 0.0001). Conclusion Percutaneous edge-to-edge MVr may be reasonable in shock patients with acute MR and/or acute MI. This case series should guide larger studies designed to improve selection of shock patients for pMVr.

Background— Destination therapy left ventricular assist devices (DT LVADs) are one of the most invasive medical interventions for end-stage illness. How patients decide whether or not to proceed with device implantation is unknown. We aimed to understand the decision-making processes of patients who either accept or decline DT LVADs. Methods and Results— Between October 2012 and September 2013, we conducted semistructured, in-depth interviews to understand patients’ decision-making experiences. Data were analyzed using a mixed inductive and deductive approach. Twenty-two eligible patients were interviewed, 15 with DT LVADs and 7 who declined. We found a strong dichotomy between decision processes with some patients (11 accepters) being automatic and others (3 accepters, 7 decliners) being reflective in their approach to decision making. The automatic group was characterized by a fear of dying and an over-riding desire to live as long as possible: “[LVAD] was the only option I had…that or push up daisies…so I automatically took this.” By contrast, the reflective group went through a reasoned process of weighing risks, benefits, and burdens: “There are worse things than death.” Irrespective of approach, most patients experienced the DT LVAD decision as a highly emotional process and many sought support from their families or spiritually. Conclusions— Some patients offered a DT LVAD face the decision by reflecting on a process and reasoning through risks and benefits. For others, the desire to live supersedes such reflective processing. Acknowledging this difference is important when considering how to support patients who are faced with this complex decision.

Ventricular tachycardia (VT) and severe heart failure (HF) are highly morbid conditions that lead to frequent hospitalization when either is uncontrolled. We sought to evaluate whether there is a difference in subsequent hospital readmissions among severe HF patients with VT undergoing ablation (Abl

BACKGROUND: Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (8,600 RPMs). Full adherence to implant techniques, heparin bridging, and pump speeds ≥9,000 RPMs resulted in a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p < 0.01) at 6 months. CONCLUSIONS: Adoption of all components of a structured surgical implant technique and clinical management strategy (PREVENT recommendations) is associated with low rates of confirmed PT.

Intractable hiccups can be a serious complication in transplant recipients. Unfortunately, many of the pharmacotherapies used to stop hiccups are associated with severe side effects as well as drug-drug interactions with immunosuppressants. We report a case of a heart transplant recipient who had had intractable hiccups for 2 months, resulting in severe insomnia, diminished appetite, and weight loss. To treat the hiccups, treatment with oral baclofen (5–10 mg 3 times daily) was started. After 6 weeks of therapy, the baclofen was titrated down and discontinued because it had not stopped the hiccups and was causing severe central nervous system side effects. Gabapentin (100 mg twice daily) was then prescribed and within 24 hours of the start of that treatment, the hiccups had resolved completely. After 3 weeks of therapy, the patient had no side effects and the gabapentin was subsequently discontinued. One year after stopping the gabapentin, the patient remains free of hiccups. Gabapentin appears to be a promising medication for the treatment of intractable hiccups in thoracic transplant recipients because of its lack of serious side effects at low doses, rapid onset of action, and lack of drug-drug interactions with transplant medications.

Heart failure (HF) is the leading cause of hospital admissions in the United States in people over the age of 65 years. Major advancements in the medical therapy of HF, combined with automatic implantable cardioverter-defibrillators and cardiac resynchronization therapy, have substantially reduced the mortality and morbidity of chronic HF, but mortality remains high, and the availability of donor hearts for transplantation is limited. Thus, there has been and continues to be a need for alternative therapies to support the failing heart. The development of mechanical pumps designed to assist or replace cardiac function started three decades ago with the National Heart, Lung, and Blood Institute's request for proposals to develop an artificial heart. Significant progress has been made, with ventricular assist devices evolving from bulky extracorporeal devices to internalized miniaturized devices. Improvements in durability, thrombogenicity, ease of implantation, and patient selection have allowed expanding indications for these devices.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by distressing sensations deep inside the limbs, typically occurring at bedtime or rest. These paresthesias involve an irresistible urge to move the limb, which provides temporary relief but at the expense of sleep and quality of life. The pathophysiology of RLS has been related to dopaminergic pathway dysfunction, thereby aligning it closely with depression from both pathophysiologic and treatment perspectives. Certain antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), may induce or exacerbate RLS. We describe the case of a 34-year-old woman with no history of RLS who came to the emergency department with acute decompensated heart failure. After 7 days of hospitalization, she was waitlisted to receive a heart transplant. Her mood became depressed, and she requested a psychiatric consultation; escitalopram 10 mg at bedtime was started. Within 2 days of starting therapy, she developed very severe (determined by a score based on an RLS symptom rating scale) RLS symptoms, warranting the discontinuation of escitalopram. Within 2 days of stopping therapy, her RLS symptoms improved considerably (rated as mild). One week later, the patient was rechallenged with a lower dose of escitalopram, and her very severe RLS symptoms reappeared. Within 2 days of stopping escitalopram, her RLS symptoms again improved, with complete resolution 1 week later. Using the Naranjo adverse drug reaction probability scale, which assesses the probability of a drug causing an adverse event, the patient's score was 9, indicating a definite adverse drug reaction. Although published case reports have linked fluoxetine, sertraline, citalopram, paroxetine, and mirtazapine to RLS, this is the first report, to our knowledge, of escitalopram as a cause of RLS. Based on this case and additional data published with other SSRIs and SNRIs, we believe that escitalopram should be added to the list of agents that can induce RLS.

Background Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1α (HIF-1α), a transcriptional factor in hypoxic signaling. Methods Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1α was measured by Western blotting with commercially available antibodies. Results Heart failure was associated with a decrease in α-myosin heavy chain and sarcoplasmic reticulum-Ca 2+ adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1α. Conclusions Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes.

Background Whipple endocarditis is caused by Tropheryma whipplei and is a well-described complication of Whipple's disease. Limited and small case series have been published regarding the presentation, diagnosis, and clinical course of this disease. Methods/Results We describe 2 cases of patients with T. whipplei endocarditis, one of which underwent a successful heart transplant. Conclusion In both cases of Whipple's endocarditis, there was a subacute prodromal phase followed by an acute rapid decompensation with severe destruction of the aortic valve, heart failure, and embolism. Because the diagnosis of T. whipplei endocarditis is typically not made until pathological examination of tissue, clinicians must have a high suspicion for it in the absence of other offending organisms, especially among middle-aged white males with sub-acute symptoms and embolic complications.

In patients with advanced heart failure, the main focus has traditionally been placed on the functional assessment of the left ventricle. Therefore, the current body of literature examining the right ventricle and its influence on the pathophysiological processes in heart failure has been limited. Methods currently employed to assess the size and function of the right ventricle include: high frequency thermodilution, contrast ventriculography, radionuclide ventriculography, echocardiography, and magnetic resonance imaging; however, none of these techniques has proven to be a 'gold standard' for the assessment of right ventricular function. Nevertheless, when these methods are employed, right ventricular dysfunction has been shown to be a powerful predictor of reduced exercise capacity and survival. This relationship holds true for patients with heart failure secondary to either ischemic or non-ischemic dilated cardiomyopathy.

Purpose of reviewThe prevalence of cardiovascular disease is markedly increased in patients with type 2 diabetes and to a somewhat lesser extent impaired glucose tolerance (IGT). This has generally been attributed to the concurrent presence of cardiovascular disease risk factors, including dyslipide

Diabetes is associated with abnormal autonomic function and increased mortality. Abnormal heart rate recovery after exercise, a measure of autonomic dysfunction, is also associated with increased mortality. The objective of this study was to determine the association of fasting plasma glucose with abnormal heart rate recovery and its prognostic importance in healthy adults. We studied 5,190 healthy adults who did not have medically treated diabetes (mean age 45 years, 39% women), were enrolled in the Lipid Research Clinics’ Prevalence Study, and underwent exercise testing. Heart rate recovery was defined as the change from peak heart rate to that after 2 min of recovery; an abnormal value was ≤42 bpm. All-cause mortality was assessed over 12 years. A total of 504 participants (10%) had impaired fasting glucose, and 131 (3%) had untreated diabetes. An abnormal heart rate recovery was found in 1,699 (33%). Compared with participants who had normal fasting plasma glucose, abnormal heart rate recovery was more common among those with impaired fasting glucose (42 vs. 31%; relative risk, 1.34; 95% confidence interval [CI], 1.20–1.50; P < 0.0001) and those with diabetes (50 vs. 31%; relative risk, 1.61; 95% CI, 1.35–1.92; P < 0.0001). Fasting plasma glucose remained an independent predictor of abnormal heart rate recovery even after adjustment for age, sex, and other confounders (P = 0.0003). An abnormal heart rate recovery added to impaired fasting plasma glucose for the prediction of death. Fasting plasma glucose is strongly and independently associated with abnormal heart rate recovery, even at nondiabetic levels.

Objectives: Venoarterial (VA) ECMO has emerged as a successful modality for bridging patients with critical cardiogenic shock to durable support. However, LV distention on ECMO impairs RV and lung recovery and can result in the need for a temporary RVAD. Additionally, patients on VA ECMO with organ dysfunction may require ongoing LV assistance for recovery prior to durable LVAD conversion. Placement of a large apical LV vent allows bedside conversion to LVAD and provides time for organ recovery prior to elective durable device implantation. Hypothesis: We hypothesized that LV venting on ECMO accelerates RV recovery, hastening conversion to LVAD. Methods: ECMO cases from January 2012 to April 2014 were reviewed following IRB approval. Sixteen patients met INTERMACS Category 1 criteria who were placed on VA ECMO for cardiogenic or post-cardiotomy shock. Eight patients had LV venting and eight had standard peripheral cannulation. Refractory pulmonary edema, CPR during cannulation, and severe LV distention were indications for LV venting. A 32 French malleable cannula was placed by limited anterolateral thoracotomy into the LV apex. Bedside LVAD conversion was performed by percutaneous decannulation of the venous line and removal of oxygenator from circuit. Results: Conversion to temporary LVAD was successful in all LV vent cases at a mean timepoint of 5.9 (±1.3) days after LV venting compared with 13.5 (±4.9) days in non-vented patients (p = 0.07). RVAD requirement was 25% in non-vented patients and 0% in vented patients. 30-day mortality was 25% for both groups. Conclusions: LV venting as an adjunct to VA ECMO facilitates RV recovery to enable early LVAD conversion at the bedside. It also provides organ recovery time and obviates the need for a temporary RVAD at the time of durable LVAD implantation. In conclusion, the LV apical venting technique allows staged recovery of critically ill patients in biventricular and multiple organ failure with a high survival rate.

Patients with continuous-flow left ventricular assist devices (LVADs) require long-term systemic anti-coagulation after implantation to prevent thrombotic events. Thrombosis of an LVADmay result in cerebrovascular accidents, device exchange or death. Over the past several years, there has been a reported increase in the risk of device thrombosis in the United States, without a clear explanation for the increase. Proper anticoagulation management in patients with an LVAD is essential for thrombosis prevention. Unfractionated heparin (UFH) is often used to bridge LVAD patients early after surgical implantation or when oral anti-coagulation is sub-therapeutic. Due to its mechanism of action, the activated partial thromboplastin time (aPTT) reflects the function of heparin’s effects on the intrinsic pathways of the coagulation cascade, whereas the anti-factor Xa (anti-Xa) assay measures heparin’s impact on anti-thrombin. The aPTT is currently the most commonly used laboratory test for monitoring UFH. A large number of variables can affect the aPTT, rendering the patient receiving UFH at risk of supraor sub-therapeutic anticoagulation. Routine monitoring of UFH using the anti-Xa assay has been reported to provide a more accurate reflection of anti-coagulation. Since the 1990s, the American College of Chest Physicians and the College of American Pathologists have recommended that aPTT goals be titrated to a corresponding anti-Xa level according to individual institutions. It is currently unknown whether the aPTT and anti-Xa levels reflect the same level of anti-coagulation in LVAD patients. Due to a higher-than-expected LVAD thrombosis rate at our institution, we hypothesized that the aPTT may not adequately reflect the level of anti-coagulation with UFH in LVAD patients; therefore, we simultaneously measured the aPTT and anti-Xa activity in both LVAD recipients and patients admitted with acute decompensated heart failure (ADHF). We performed a prospective, single-center quality improvement project that included all hospitalized patients receiving

Background: Patients offered left ventricular assist device as destination therapy (DT LVAD) are typically faced with the decision to undergo major surgery and live their remaining life dependent on mechanical circulatory support (MCS) or transition to end-of-life care. MCS coordinators are often the first point of contact and provide education and support to patients making this difficult decision. Methods: We conducted semi-structured, in-depth interviews with MCS coordinators in order to characterize the range of decision support and preparation offered to patients considering DT LVAD and to solicit input on how to optimize that process. Interviews took place from August 2012 to January 2013. All interviews were digitally recorded and data were analyzed using a directed content analysis approach. Results: Our sample included 20 MCS coordinators from different programs around the United States. The following primary themes emerged: 1) cardiothoracic surgeons or heart failure cardiologists were primarily responsible for presenting risks and benefits of DT LVAD whereas coordinators provided the majority of patient education regarding practical concerns and patient/caregiver responsibilities; 2) existing consents and industry material are too complicated or overly optimistic; 3) tension exists between creating accurate expectations of DT LVADs and providing clinical reassurance - “I don’t want to scare them away from a life-saving therapy either, so I try to paint a realistic picture but not so realistic that it scares them;” and 4) when asked to theoretically consider if they were offered DT LVAD, the majority of coordinators stated that it would be a difficult decision influenced by their own age, co-morbidities, and family dynamics - “I think it would really depend on where I was in my life at that point in time.” Conclusions: MCS coordinators are in a unique position to assist in decision making and preparation for patients eligible for DT LVADs. In order to improve this process, a multidisciplinary and iterative approach appears helpful in conveying the risks and benefits of DT LVAD. Consents and educational materials must be simplified, patient-centered, and free of bias. Patient needs and values should be defined up front to help tailor the process. The uncertainty of many MCS coordinators, who arguably best understand the totality of therapy, to theoretically pursue DT LVAD themselves highlights the difficult trade-offs and personalized nature of this decision.

Background: Left ventricular assist device as destination therapy (DT LVAD) is an option for some transplant ineligible patients who are actively dying of heart failure. Essentially, patients are faced with the decision to undergo major surgery to implant a partial artificial heart or transition to end-of-life care. While LVADs can extend life, they are also associated with significant risks including infection, stroke, and caregiver burden. How patients make this decision is poorly understood. Methods: We performed semi-structured, in-depth interviews based on the Ottawa Decision Support Framework to understand patients’ decisional needs in accepting or declining DT LVAD. All patients who had DT LVAD in place and patients who declined DT LVAD at an academic medical center between October-December 2012 were interviewed. Interviews were audio-recorded and transcribed. Data were analyzed using a mixed inductive and deductive approach. Additionally, we measured decision regret using the validated, 5-item decision regret scale. Results: All 17 eligible patients were interviewed, 13 with DT LVADs and 4 who had declined. Their mean age was 68. Patients accepting DT LVADs often did not perceive a decision. “I had to do it if I wanted to exist anymore.” This perception appeared to come from a belief that choosing end-of-life medical care was not an option, “This [LVAD] was the only option I had..that or push up daisies...so I automatically took this.” They also noted that the risks of the LVAD were not that important as they had “nothing to lose.” Those who declined an LVAD stated they were not afraid of death, asserted that their life lived had meaning, and recognized the potential burdens to both themselves and their family, “There are worse things than death.” For both accepters and decliners, this was an emotionally and spiritually driven decision. Both groups felt highly involved and informed. They also endorsed little decision regret (mean 5/100 for acceptors, 0/100 for decliners). Conclusions: There is a fundamental difference in values surrounding death among patients who either accept or decline a DT LVAD. Decision support interventions around this complex medical decision need to consider patient values first before getting into more cognitive aspects of the decision making process.

Background: The use of calcineurin inhibitors revolutionized transplantation by prolonging patients’ survival. However, their utility is limited by the development of significant chronic kidney disease. Methods: We reviewed the English literature looking for recent publications regarding the management of chronic kidney disease in cardiac transplant patients. We chose relevant papers based on design, number of patients and clinical utility. Results: Most publications on the subject involve small populations with few prospective, randomized studies. Early use of tacrolimus appears to be associated with better kidney function after one year compared to cyclosporine. Once chronic kidney disease is established, successful strategies include reduction or elimination of calcineurin inhibitors while relying on mycophenolate mofetil, proliferation signal inhibitors or anti-CD 25 antibodies to prevent rejection. There is no follow up longer than two years with these approaches. Kidney transplantation might offer improved long-term survival compared to dialysis in end-stage disease. Conclusions: Prospective studies with long-term follow-up are needed to decide about the timing and to confirm the utility of replacing calcineurin inhibitors with other agents in cardiac transplant patients with chronic kidney disease.