Minimally invasive biventricular mechanical circulatory support with Impella pumps as a bridge to heart transplantation: a first-in-the-world case report.

Cardiogenic shock from biventricular failure that requires acute mechanical circulatory support carries high 30 day mortality. Acute mechanical circulatory support can serve as bridge to orthotopic heart transplant (OHT) in selected patients. We report a patient with biventricular failure secondary to rapidly progressive cardiac sarcoidosis refractory to medical management who was bridged to OHT with Impella 5.0 and Impella RP-temporary left and right ventricular assist devices, respectively. This is the first successful bridge to transplantation using these devices in biventricular heart failure and cardiogenic shock. We discuss considerations for using this strategy over veno-arterial extracorporeal membrane oxygenation or surgically implanted assist devices in patients with cardiogenic shock and biventricular failure as a bridge to OHT.

Burden and consequences of retained cardiovascular implantable electronic device lead fragments after heart transplantation.

We performed a retrospective review of 402 consecutive patients who underwent heart transplantation at our institution between January 2009 and March 2017. A retained cardiovascular implantable electronic device (CIED) fragment was identified after transplantation in 49 of the 301 patients (16.2%) with CIED at baseline. Patients with retained fragments had leads with longer dwell times (median 2596 [1982, 3389] vs 1384 [610, 2202] days, P < .001), higher prevalence of previously abandoned leads (14.3% vs 2.8%, P = .003), and dual-coil defibrillator leads (98% vs 81%, P = .001) compared with patients without retained fragments. Five patients (10%) with retained CIED fragments underwent magnetic resonance imaging without adverse events. There was no difference in overall mortality between patients with and without CIED fragments (12% vs 11%, P = .81) Patients with retained fragments located in the superior vena cava had significantly higher fluoroscopic times (3.3 vs 2.9 minutes, P = .024) during subsequent endomyocardial biopsies. In a competing risk analysis, presence of a retained CIED fragment was associated with upper extremity deep venous thrombosis (sub hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.17-4.10, P = .014) but not bloodstream infection after adjusting for potential confounders. In summary, retained CIED fragments are common after heart transplantation, and are associated with longer radiation exposure during biopsy procedures and upper extremity deep venous thrombosis.

Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure.

BACKGROUND: Lower serum chloride (Cl) is associated with mortality in heart failure patients and may be more prognostically relevant than sodium. However, the association of hemodynamics and Cl levels is unknown. METHODS: 438 sequential patients with advanced chronic heart failure (ACHF) underwent invasive hemodynamic assessment with measured serum Cl levels during an evaluation for ACHF. Patients were followed for death, heart transplant (HT), or ventricular assist device placement (VAD). A backwards regression model determined hemodynamic predictors of Cl (removal, P<0.1) with candidate variables: Fick cardiac index (FCI), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), mean arterial pressure (MAP), heart rate (HR), and pulmonary artery systolic pressure (PASP). All models were also adjusted for serum sodium and bicarbonate. RESULTS: In this cohort, the median Cl level was 102 [98-104]meq/L (range 86-113meq/L). Chloride was weakly correlated with FCI (rho 0.12, P=0.01) and MAP (rho 0.21, P<0.001); but not PCWP, RAP, HR or PASP (P>0.05 for all). In the multivariable model, FCI (beta 0.73meq/L/L/min/m2, P=0.002) but not RAP (P=0.3) or MAP (P=0.2), remained associated with Cl. Lower Cl was associated with increased risk of death, HT, or VAD placement (HR 0.94/meq/L, 95% CI 0.89-0.99, P=0.01). However, this association was attenuated after additional adjustment for BUN (P=0.27) and PCWP and FCI (0.48). CONCLUSIONS: Lower FCI, not lower MAP or higher cardiac filling pressures, was associated with lower chloride. Although lower chloride was associated with poor long-term outcomes, this risk attenuates with adjustment for more conventional clinical parameters.

Discordance between 'actual' and 'scheduled' check-in times at a heart failure clinic.

INTRODUCTION: A 2015 Institute Of Medicine statement "Transforming Health Care Scheduling and Access: Getting to Now", has increased concerns regarding patient wait times. Although waiting times have been widely studied, little attention has been paid to the role of patient arrival times as a component of this phenomenon. To this end, we investigated patterns of patient arrival at scheduled ambulatory heart failure (HF) clinic appointments and studied its predictors. We hypothesized that patients are more likely to arrive later than scheduled, with progressively later arrivals later in the day. METHODS AND RESULTS: Using a business intelligence database we identified 6,194 unique patients that visited the Cleveland Clinic Main Campus HF clinic between January, 2015 and January, 2017. This clinic served both as a tertiary referral center and a community HF clinic. Transplant and left ventricular assist device (LVAD) visits were excluded. Punctuality was defined as the difference between 'actual' and 'scheduled' check-in times, whereby negative values (i.e., early punctuality) were patients who checked-in early. Contrary to our hypothesis, we found that patients checked-in late only a minority of the time (38% of visits). Additionally, examining punctuality by appointment hour slot we found that patients scheduled after 8AM had progressively earlier check-in times as the day progressed (P < .001 for trend). In both a Random Forest-Regression framework and linear regression models the most important risk-adjusted predictors of early punctuality were: later in the day appointment hour slot, patient having previously been to the hospital, age in the early 70s, and white race. CONCLUSIONS: Patients attending a mixed population ambulatory HF clinic check-in earlier than scheduled times, with progressive discrepant intervals throughout the day. This finding may have significant implications for provider utilization and resource planning in order to maximize clinic efficiency. The impact of elective early arrival on patient's perceived wait times requires further study.

Association of recipient age and causes of heart transplant mortality: Implications for personalization of post-transplant management-An analysis of the International Society for Heart and Lung Transplantation Registry.

BACKGROUND: Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established. METHODS: We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups. RESULTS: There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important. CONCLUSIONS: Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival.

Impact of Statin Use After Heart Transplantation: A Meta-Analysis.

BACKGROUND: Although various studies revealed the beneficial effects of statins in post-cardiac transplant patients, these were relatively small and low-powered studies. We performed a meta-analysis of published studies to evaluate the role of statins in post-cardiac transplant patients, specifically examining the effects on hemodynamically significant/fatal graft rejection, coronary vasculopathy, terminal cancer, and overall survival. METHODS AND RESULTS: We searched PubMed, Cochran CENTRAL, and Web of Science databases using the search terms "cardiac transplant" or "heart transplant," and "statin" for a literature search. A random-effects model with Mantel-Haenszel method was used to pool the data. We identified 10 studies, 4 randomized controlled trials, and 6 nonrandomized studies, which compared outcomes in heart transplant recipients undergoing statin therapy to statin-naive patients. A pooled analysis of 9 studies reporting mortality revealed that the use of statins was associated with significant reduction in all-cause mortality (odds ratio, 0.26; 95% confidence interval, 0.20-0.35; P<0.0001). Statins also decreased the odds of hemodynamically significant/fatal rejection (odds ratio, 0.37; 95% confidence interval, 0.21-0.65; P=0.0005), incidence of coronary vasculopathy (odds ratio, 0.33; 95% confidence interval, 0.16-0.68; P=0.003), and terminal cancer (odds ratio, 0.30; 95% confidence interval, 0.15-0.63; P=0.002). CONCLUSIONS: The evidence from a pooled analysis suggests that statins improve survival in heart transplant recipients. Statins may prevent fatal rejection episodes, decrease terminal cancer risk, and reduce the incidence of coronary vasculopathy. Additional prospective studies are needed to further investigate and explain this association.

Does Survival on the Heart Transplant Waiting List Depend on the Underlying Heart Disease?

OBJECTIVES: The aim of this study was to identify differences in survival on the basis of type of heart disease while awaiting orthotopic heart transplantation (OHT). BACKGROUND: Patients with restrictive cardiomyopathy (RCM), congenital heart disease (CHD), or hypertrophic cardiomyopathy (HCM) may be at a disadvantage while awaiting OHT because they often are poor candidates for mechanical circulatory support and/or inotropes. METHODS: The study included all adults in the Scientific Registry of Transplant Recipients database awaiting OHT from 2004 to 2014, and outcomes were evaluated on the basis of type of heart disease. The primary endpoint was time to all-cause mortality, censored at last patient follow-up and time of transplantation. Multivariate Cox proportional hazards modeling was performed to evaluate survival by type of cardiomyopathy. RESULTS: There were 14,447 patients with DCM, 823 with RCM, 11,799 with ischemic cardiomyopathy (ICM), 602 with HCM, 964 with CHD, 584 with valvular disease, and 1,528 in the "other" category (including 1,216 for retransplantation). During median follow-up of 3.7 months, 4,943 patients died (1,253 women, 3,690 men). After adjusting for possible confounding variables including age, renal function, inotropes, mechanical ventilation, and mechanical circulatory support, the adjusted hazard ratios by diagnoses relative to DCM were 1.70 for RCM (95% confidence interval [CI]: 1.43 to 2.02), 1.10 for ICM (95% CI: 1.03 to 1.18), 1.23 for HCM (95% CI: 0.98 to 1.54), 1.30 for valvular disease (95% CI: 1.07 to 1.57), 1.37 for CHD (95% CI: 1.17 to 1.61), and 1.51 for "other" diagnoses (95% CI: 1.34 to 1.69). Sex was a significant modifier of mortality for ICM, RCM, and "other" diagnoses (p < 0.05 for interaction). CONCLUSIONS: In the United States, patients with RCM, CHD, or prior heart transplantation had a higher risk for death while awaiting OHT than patients with DCM, ICM, HCM, or valvular heart disease.

Transient Hyponatremia During Hospitalization for Acute Heart Failure.

OBJECTIVE: The objective was to study whether the temporal pattern of transient hyponatremia development in acute heart failure might provide insight into its pathophysiology and prognostic relevance. METHODS: A post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE AHF) studies was performed (n = 716). Patients were stratified according to the temporal pattern of hyponatremia development: (1) no hyponatremia, (2) persistent hyponatremia, (3) decompensation hyponatremia disappearing with decongestive treatment, and (4) treatment-induced hyponatremia. RESULTS: Transient decompensation versus no hyponatremia was associated with significantly elevated blood urea nitrogen/creatinine ratio (P < .001), plasma renin activity (P < .001), and plasma aldosterone levels (P < .001) at baseline. Disease severity characteristics of such patients were intermediate between no and persistent hyponatremia. In contrast, patients with treatment-induced versus no hyponatremia had similar baseline characteristics and comparable natriuretic peptide levels, and both groups had little neurohumoral activation at baseline. Diuretic efficacy, defined as net fluid balance (milliliters) per 40 mg furosemide-equivalent dose administered, was lower in patients with persistent or treatment-induced hyponatremia versus decompensation hyponatremia or no hyponatremia, respectively. The former versus latter groups also had more pronounced neurohumoral activation with decongestive treatment. The risk for all-cause mortality (hazard ratio, 2.50; 95% confidence interval, 1.50-4.19; P < .001) and death or heart failure readmission (hazard ratio, 2.18; 95% confidence interval, 1.60-2.97; P < .001) was significantly elevated in patients with persistent versus no hyponatremia, with the risk of decompensation and treatment hyponatremia situated in between. CONCLUSIONS: Transient hyponatremia is prognostically relevant, but it has a heterogeneous cause according to its temporal pattern of development.

A 39-Year-Old Postpartum Woman With Foot Drop and Shortness of Breath.

A 39-year-old white woman with a history of adult-onset asthma, chronic sinusitis, and nasal polyposis presented to the ED with dyspnea and left lower extremity weakness and pain. Three months prior to her presentation she had an uncomplicated delivery of her second child, but during her pregnancy she experienced increasing asthma symptoms and nasal congestion. These symptoms progressed after delivery despite treatment with albuterol inhalers and antibiotics.

A new class of drugs for systolic heart failure: The PARADIGM-HF study.

The PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found a combination drug containing sacubitril (a neprilysin inhibitor) and valsartan (an angiotensin II receptor blocker) superior to enalapril (an angiotensin-converting enzyme inhibitor) in patients with systolic heart failure. Recently approved by the US Food and Drug Administration, sacubitril-valsartan is the first new drug in over a decade to decrease death rates in patients with systolic heart failure.

Long-term dietary habits and interventions in solid-organ transplantation.

Diet and nutrition are moving to the forefront of modern primary and preventive care to help address the rising burden of chronic diseases among the general population. Such a movement has yet to occur formally across the field of transplantation. We therefore looked to establish the current base of knowledge regarding diet, nutrition and solid-organ transplantation. A limited number of focused studies looking into the dietary habits of solid-organ transplant patients have been performed and many of the available studies have detailed the nutritional status in the peri-operative period. Frequently described, however, is the heavy incidence of metabolic abnormalities, such as obesity, dyslipidemia and diabetes, occurring after solid-organ transplantation. Optimistically, several studies have noted improvement in several metabolic abnormalities with the use of dietary interventions in the post-transplant period. Despite these positive results, few consensus guidelines for post-transplant diet have been established and nutritional support among transplant programs remains limited. Although there are many hurdles to implementation of detailed dietary recommendations and nutritional support for transplant patients, creating such programs and guidelines could dramatically impact long-term outcomes and burden of chronic metabolic disease for transplant recipients.

Response and tolerance to oral vasodilator up-titration after intravenous vasodilator therapy in advanced decompensated heart failure.

AIMS: The aim of this study was to assess the haemodynamic response and tolerance to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) up-titration after intravenous vasodilator therapy in advanced decompensated heart failure (ADHF). METHODS AND RESULTS: Medical records of 147 consecutive ADHF patients who underwent placement of a pulmonary artery catheter and received intravenous vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium nitroglycerin as first-line agent for those with preserved blood pressures were utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were converted to oral HYD/ISDN combination therapy through a standardized conversion protocol. These patients had a significantly higher admission mean pulmonary arterial wedge pressure compared with patients not converted (28 ± 7 vs. 25 ± 8 mmHg, respectively; P-value 0.024). Beneficial haemodynamic response to decongestive therapy, defined as low cardiac filling pressures and cardiac index ≥2.20 L/min/m(2) without emergent hypotension, was achieved in 32% and 29% of patients who did or did not receive oral HYD/ISDN, respectively (P-value 0.762). HYD/ISDN dosing was progressively and consistently decreased up to the moment of hospital discharge and during outpatient follow-up, primarily due to incident hypotension. CONCLUSION: The use of a standardized haemodynamically guided up-titration protocol for conversion from intravenous to oral vasodilators may warrant subsequent dose reductions upon stabilization.

Advances in the understanding and management of heart transplantation.

Cardiac transplantation represents one of the great triumphs in modern medicine and remains the cornerstone in the treatment of advanced heart failure. In this review, we contextualize pivotal developments in our understanding and management of cardiac transplant immunology, histopathology, rejection surveillance, drug development and surgery. We also discuss current limitations in their application and the impact of the left ventricular assist devices in bridging this gap.

A disproportionate elevation in right ventricular filling pressure, in relation to left ventricular filling pressure, is associated with renal impairment and increased mortality in advanced decompensated heart failure.

BACKGROUND: Discordance between left- and right-sided filling pressures occurs in a subset of patients presenting with acute decompensated heart failure (ADHF). We hypothesized that a disproportionately increased right atrial pressure (RAP) relative to the pulmonary capillary wedge pressure (PCWP) would be associated with both renal dysfunction and mortality in ADHF. METHODS: A total of 367 patients admitted with ADHF with elevated intracardiac filling pressures were treated with intensive medical therapy guided by invasive hemodynamic monitoring. Baseline characteristics, hemodynamics, and renal function at admission were stratified by RAP/PCWP quartiles. The association of RAP/PCWP quartile with all-cause mortality after a median follow-up of 2.4 years was assessed in univariable and multivariable models, which included adjustment for the RAP. RESULTS: The median RAP/PCWP was 0.58 (interquartile range 0.43-0.75). Increasing RAP/PCWP was inversely associated with estimated glomerular filtration rate at baseline and with treatment (P < .0001) independently of RAP. High RAP/PCWP was associated with increased mortality (quartile 4 vs 1: hazard ratio [95% CI] 2.1 [1.3-3.5], P = .002). The association of RAP/PCWP with mortality persisted after adjustment for age, gender, mean arterial pressure, RAP, cardiac index, pulmonary vascular resistance, and estimated glomerular filtration rate (hazard ratio 2.4 [1.4-3.9], P = .007). CONCLUSION: A disproportionate increase in right to left ventricular filling pressures is associated with renal dysfunction and mortality, independently of the right atrial pressure.

Prognostic role of cardiac power index in ambulatory patients with advanced heart failure.

BACKGROUND: Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. METHODS AND RESULTS: We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (<0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P < 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). CONCLUSION: Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors.