Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality, but the identification of LVAD candidates at risk for ...RVF remains challenging. We undertook a systematic review and meta‐analysis of observational studies of risk factors associated with RVF after LVAD implant. Thirty‐six studies published between 1 January 1995 and 30 April 2015, comprising 995 RVF patients out of a pooled final population of 4428 patients, were identified. Meta‐analysed prevalence of post‐LVAD RVF was 35%. A need for mechanical ventilation odds ratio (OR) 2.99, or continuous renal replacement therapy (CRRT; OR 4.61, area under the curve 0.78, specificity 0.91) were the clinical variables with the highest effect size (ES) in predicting RVF. International normalized ratio INR; standardized mean difference (SMD) 0.49 and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) (SMD 0.52) were the biochemical markers that best discriminated between RVF and No‐RVF populations, though NT‐proBNP was highly heterogeneous. Right ventricular stroke work index (RVSWI) and central venous pressure (CVP) (SMD −0.58 and 0.47, respectively) were the haemodynamic measures with the highest ES in identifying patients at risk of post‐LVAD RVF; CVP was particularly useful in risk stratifying patients undergoing continuous‐flow LVAD implant (SMD 0.59, P < 0.001, I2 = 20.9%). Finally, pre‐implant moderate to severe right ventricular (RV) dysfunction, as assessed qualitatively (OR 2.82), or a greater RV/LV diameter ratio (SMD 0.51) were the standard echocardiographic measurements with the highest ES in comparing RVF with No‐RVF patients. Longitudinal systolic strain of the RV free wall had the highest ES (SMD 0.73) but also the greatest heterogeneity (I2 = 74%) and was thus only marginally significant (P = 0.05). Patients on ventilatory support or CRRT are at high risk for post‐LVAD RVF, similarly to patients with slightly increased INR, high NT‐proBNP or leukocytosis. High CVP, low RVSWI, an enlarged right ventricle with concomitant low RV strain also identify patients at higher risk.
Objectives The purpose of this study was to determine the occurrence and causes of readmissions after implantation of axial flow left ventricular assist device (LVAD). Background Based on the REMATCH ...(Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) study experience, readmissions after LVAD implantation are thought to be frequent. Methods We retrospectively analyzed admissions to our facility in a cohort of 115 patients implanted between January 2008 and July 2011 with the HeartMate II axial flow LVAD, of whom 42 were bridged to transplant. To account for repeated events, Andersen-Gill models were used to determine possible predictors. Results The patients were followed for 1.4 ± 0.9 years. There were 224 readmissions in 83 patients. The overall readmission rate was 1.64 ± 1.97 per patient-year of follow-up. The readmission rate for the first 6 months was 2.0 ± 2.3 and decreased to 1.2 ± 2.1 during subsequent follow-up. Leading causes were bleeding (66 readmissions in 34 patients), mostly gastrointestinal bleed (51 in 27 patients), cardiac (51 in 36 patients, most for HF or arrhythmia), infections (32 in 25 patients) of which 6 were pump related, and thrombosis (20 in 15 patients) including 13 readmissions due to hemolysis. Preoperative variables associated with (fewer) readmissions in a multivariate model include residence within our hospital-extended referral zone of Minnesota and the neighboring states (hazard ratio: 0.66; 95% confidence interval: 0.48 to 0.91; p = 0.011), hemoglobin (hazard ratio: 0.91, 95% confidence interval: 0.84 to 0.99; p = 0.027) and N-terminal pro–B-type natriuretic peptide (hazard ratio: 0.98; 95% confidence interval: 0.96 to 1.0 per 1,000-unit increase, p = 0.022). C-statistic for the model: 0.63. Conclusions Readmission rates after axial flow LVAD implantation decrease during the first 6 months and then stabilize. The leading causes are bleeding, cardiac (heart failure and arrhythmia), infections, and thrombosis.
Frailty is recognized as a major prognostic indicator in heart failure. There has been interest in understanding whether pre-operative frailty is associated with worse outcomes after implantation of ...a left ventricular assist device (LVAD) as destination therapy.
Patients undergoing LVAD implantation as destination therapy at the Mayo Clinic, Rochester, Minnesota, from February 2007 to June 2012, were included in this study. Frailty was assessed using the deficit index (31 impairments, disabilities and comorbidities) and defined as the proportion of deficits present. We divided patients based on tertiles of the deficit index (>0.32 = frail, 0.23 to 0.32 = intermediate frail, <0.23 = not frail). Cox proportional hazard regression models were used to examine the association between frailty and death. Patients were censored at death or last follow-up through October 2013.
Among 99 patients (mean age 65 years, 18% female, 55% with ischemic heart failure), the deficit index ranged from 0.10 to 0.65 (mean 0.29). After a mean follow-up of 1.9 ± 1.6 years, 79% of the patients had been rehospitalized (range 0 to 17 hospitalizations, median 1 per person) and 45% had died. Compared with those who were not frail, patients who were intermediate frail (adjusted HR 1.70, 95% CI 0.71 to 4.31) and frail (HR 3.08, 95% CI 1.40 to 7.48) were at increased risk for death (p for trend = 0.004). The mean (SD) number of days alive out of hospital the first year after LVAD was 293 (107) for not frail, 266 (134) for intermediate frail and 250 (132) for frail patients.
Frailty before destination LVAD implantation is associated with increased risk of death and may represent a significant patient selection consideration.
The aim of this study was to assess whether serial quantitative assessment of right ventricular (RV) function by speckle-based strain imaging is affected by pulmonary hypertension–specific therapies ...and whether there is a correlation between serial changes in RV strain and clinical status. RV longitudinal systolic function was assessed using speckle-tracking echocardiography in 50 patients with pulmonary arterial hypertension (PAH) before and after the initiation of therapy. The mean interval to follow-up was 6 ± 2 months. Subsequent survival was assessed over 4 years. Patients demonstrated a mean increase in RV systolic strain from −15 ± 5 before to −20 ± 7% (p = 0.0001) after PAH treatment. Persistence of or progression to a severe reduction in free wall systolic strain (<−12.5%) at 6 months was associated with greater disease severity (100% were in functional class III or IV vs 42%, p = 0.005), greater diuretic use (86% vs 40%, p = 0.02), higher mean pulmonary artery pressure (67 ± 20 vs 46 ± 17 mm Hg, p = 0.006), and poorer survival (4-year mortality 43% vs 23%, p = 0.002). After adjusting for age, functional class, and RV strain at baseline, patients with ≥5% improvement in RV free wall systolic strain had a greater than sevenfold lower mortality risk at 4 years (hazard ratio 0.13, 95% confidence interval 0.03 to 0.50, p = 0.003). In conclusion, serial echocardiographic assessment of RV longitudinal systolic function by quantitative strain imaging independently predicts clinical deterioration and mortality in patients with PAH after the institution of medical therapy.
ABSTRACTThe mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Several recent clinical trials have demonstrated their ...efficacy in combination with reduced cyclosporine dosing in de novo heart transplant recipients, in particular with everolimus. A number of other studies have demonstrated their efficacy for improving renal function and reducing calcineurin inhibitor use, attenuating cardiac allograft vasculopathy progression and reducing cytomegalovirus infections in maintenance heart transplant populations. A growing body of literature, including a small number of clinical trials, now describes the use mTOR inhibitors in lung transplant recipients. The benefits in this population include improved lung and renal function in limited studies. Considerably less evidence is available in pediatric heart transplantation, though similar indications in the maintenance therapy population have been described. The benefits of mTOR inhibitors must be weighed against the increased risk of adverse events and drug intolerance compared with other primary immunosuppressants, and discontinuation rates are particularly high in lung transplant recipients. The risks of surgical wound healing complications in transplant recipients receiving mTOR inhibitors previously or actively supported by mechanical circulatory support devices remains poorly described in the current literature. The current role and recent evidence for mTOR inhibitor use in heart and lung transplantation is examined in this review.
In light of the updated lowered threshold for diagnosing pulmonary hypertension (PH), the reversibility of precapillary PH with left ventricular assist device (LVAD) and the associated post-heart ...transplantation (HT) outcomes remain unclear.
Using data from the United Network for Organ Sharing database, we aimed to investigate predictors of persistent precapillary PH in HT recipients bridged with LVAD and examine the interrelated post-HT survival using the updated pulmonary vascular resistance (PVR) cutoff of >2 Wood units for precapillary PH.
Among 2169 HT recipients bridged with LVAD, 1299 had PVR >2 at baseline; 551 (42.4%) of whom normalized their PVR ≤2 and 748 (57.6%) remained with elevated PVR >2 after LVAD implantation. Female sex (adjusted odds ratio aOR; 2.22, 95% confidence interval CI, 1.61-3.07; P < .001) and inotrope treatment at listing (aOR, 1.31; 95% CI, 1.03-1.66; P = .028) were associated with persistently elevated PVR after LVAD. Conversely, longer duration of LVAD support (aOR, 0.74; 95% CI, 0.65-0.84; P < .001) and use of HeartMate II (aOR, 0.74; CI, 0.59-0.93; P = .011) were found to be protective against persistently elevated PVR after LVAD. Persistently elevated PVR >2 after LVAD was associated with increased risk of death compared with those who normalized their PVR (adjusted hazard ratio aHR, 1.26; 95% CI, 1.01-1.57; P = .037). However, the normalized PVR post-LVAD group had comparable survival with those with PVR ≤2 at baseline (aHR, 0.76; 95% CI, 0.57-1.02; P = .07).
Many recipients of HT bridged with LVAD remain with PVR >2 after LVAD implantation, which is associated with increased risk of death after HT compared with patients with normalized PVR after LVAD.
Objectives This study sought to evaluate the risk of cancer in patients with heart failure (HF) compared with community controls and to determine the impact of cancer post-HF on outcomes. Background ...HF is associated with excess morbidity and mortality. Noncardiac causes of adverse outcomes in HF are increasingly recognized, but not fully characterized. Methods In a case-control study, we compared the history of cancer among community subjects newly diagnosed with HF from 1979 to 2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at the index date (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed. Results Before the index date, 22% of HF cases and 23% of controls had a history of cancer (odds ratio OR: 0.94; 95% confidence interval CI: 0.75 to 1.17). During 9,203 person-years of follow-up (7.7 ± 6.4 years), 244 new cancer cases were identified; HF patients had a 68% higher risk of developing cancer (hazard ratio HR: 1.68; 95% CI: 1.13 to 2.50) adjusted for body mass index, smoking, and comorbidities. The HRs were similar for men and women, with a trend toward a stronger association among subjects ≤75 years of age (p = 0.22) and during the most recent time period (p = 0.075). Among HF cases, incident cancer increased the risk of death (HR: 1.56; 95% CI: 1.22 to 1.99) adjusted for age, sex, index year, and comorbidities. Conclusions HF patients are at increased risk of cancer, which appears to have increased over time. Cancer increases mortality in HF, underscoring the importance of noncardiac morbidity and of cancer surveillance in the management of HF patients.
Objectives The aim of this study was to determine renal outcomes after left ventricular assist device (LVAD) implantation. Background Renal dysfunction before LVAD placement is frequent, and it is ...unclear whether it is due to primary renal disease or to poor perfusion. Methods A retrospective single-center analysis was conducted in 83 consecutive patients implanted with HeartMate II continuous-flow LVADs (Thoratec Corp., Pleasanton, California). Calculated glomerular filtration rate (GFR) was assessed on admission and 1, 3, and 6 months after implantation. To define predictors for improvement in GFR, clinical variables were examined in patients with decreased renal function (GFR <60 ml/min/1.73 m2 ) before LVAD, surviving and dialysis-free at 1 month (n = 44). Results GFR significantly increased from admission (53.2 ± 21.4 ml/min/1.73 m2 ) to 1 month after LVAD implantation (87.4 ± 27.9 ml/min/1.73 m2 ) (p < 0.0001). Subsequently, at 3 and 6 months, GFR remained significantly (p < 0.0001) above pre-LVAD values. Of the 51 patients with GFRs <60 ml/min/1.73 m2 before LVAD surviving at 1 month, 34 (67%) improved to GFRs >60 ml/min/1.73 m2 . Univariate pre-operative predictors for improvement in renal function at 1 month included younger age (p = 0.049), GFR improvement with optimal medical therapy (p < 0.001), intra-aortic balloon pump use (p = 0.004), kidney length above 10 cm (p = 0.023), no treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.029), higher bilirubin (p = 0.002), higher Lietz-Miller score (p = 0.019), and atrial fibrillation (p = 0.007). Multivariate analysis indicated pre-operative improved GFR (slope = 0.5 U per unit improved; 95% confidence interval: 0.2 to 0.8; p = 0.003), atrial fibrillation (slope = 27; 95% confidence interval: 8 to 46; p = 0.006), and intra-aortic balloon pump use (slope = 14; 95% confidence interval: 2 to 26; p = 0.02) as independent predictors. Conclusions In most patients with end-stage heart failure considered for LVAD implantation, renal dysfunction is reversible and likely related to poor renal perfusion.