Abstract Background The number of centers with left ventricular assist device (LVAD) research programs focused on cardiac recovery is very small. Therefore, this phenomenon has been reported in ...real-world multi-center registries as a rare event. Objectives This study evaluated the incidence of cardiac recovery with an a priori LVAD implantation strategy of bridge-to-recovery (BTR) and constructed a recovery predictive model. Methods The study included LVAD recipients registered in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Cardiac recovery was evaluated in BTR and non-BTR patients. A weighted score was derived and externally validated in patients of the Utah Cardiac Recovery (UCAR) program. Results Of 15,138 INTERMACS patients, cardiac recovery occurred in 192 (1.3%). The incidence of recovery was 11.2% (n = 14) in BTR compared with 1.2% (n = 178) in non-BTR patients (p < 0.0001). Independent predictors of recovery included: age <50 years, non-ischemic cardiomyopathy, time from cardiac diagnosis <2 years, absence of ICD, creatinine ≤1.2 mg/dl, and LVEDD <6.5 cm (c-index: 0.85; p < 0.0001). A weighted score termed I-CARS, effectively stratified patients based on their probability of recovery. I-CARS was validated in the UCAR cohort (n = 190) with good performance (AUC: 0.94; 95% CI: 0.91 to 0.98). One-year survival after LVAD explantation, available in INTERMACS for 21 (11%) patients, was 86%. Conclusions The incidence of cardiac recovery is higher in patients implanted with an a priori BTR strategy. We developed a simple tool to help identify patients in whom recovery is feasible. In BTR patients with favorable characteristics, I-CARS suggests a 24% probability of successful LVAD explantation. Large-scale studies to better address post-explantation outcomes are warranted.
Progress in precision medicine is limited by insufficient knowledge of transcriptomic or proteomic features in involved tissues that define pathobiological differences between patients. Here, ...myectomy tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure is analyzed using RNA-Seq, and the results are used to develop individualized protein-protein interaction networks. From this approach, hypertrophic cardiomyopathy is distinguished from dilated cardiomyopathy based on the protein-protein interaction network pattern. Within the hypertrophic cardiomyopathy cohort, the patient-specific networks are variable in complexity, and enriched for 30 endophenotypes. The cardiac Janus kinase 2-Signal Transducer and Activator of Transcription 3-collagen 4A2 (JAK2-STAT3-COL4A2) expression profile informed by the networks was able to discriminate two hypertrophic cardiomyopathy patients with extreme fibrosis phenotypes. Patient-specific network features also associate with other important hypertrophic cardiomyopathy clinical phenotypes. These proof-of-concept findings introduce personalized protein-protein interaction networks (reticulotypes) for characterizing patient-specific pathobiology, thereby offering a direct strategy for advancing precision medicine.
Abstract Background Small-scale studies focused mainly on nonischemic cardiomyopathy (NICM) have shown that a subset of left ventricular assist device (LVAD) patients can achieve significant ...improvement of their native heart function, but the impact of ischemic cardiomyopathy (ICM) has not been specifically investigated. Many patients with acute myocardial infarction are discharged from their index hospitalization without heart failure (HF), only to return much later with overt HF syndrome, mainly caused by chronic remodeling of the noninfarcted region of the myocardium. Objectives This study sought to prospectively investigate the effect of ICM HF etiology on LVAD-associated improvement of cardiac structure and function using NICM as control. Methods Consecutive patients (n = 154) with documented chronic and dilated cardiomyopathy (ICM, n = 61; NICM, n = 93) requiring durable support with continuous-flow LVAD were prospectively evaluated with serial echocardiograms and right heart catheterizations. Results In patients supported with LVAD for at least 6 months, we found that 5% of subjects with ICM and 21% of subjects with NICM achieved left ventricular ejection fraction ≥40% (p = 0.034). LV end-diastolic and end-systolic volumes and diastolic function were significantly and similarly improved in patients with ICM and NICM. Conclusions LVAD-associated unloading for 6 months resulted in a substantial improvement in myocardial structure, and systolic and diastolic function in 1 in 20 ICM and 1 in 5 NICM patients. These specific incidence and timeline findings may provide guidance in clinical practice and research design for sequencing and prioritizing advanced HF and heart transplantation therapeutic options in patients with ICM and NICM.
Objective
To identify predictors of 30‐day all‐cause mortality for patients with cardiogenic shock secondary to acute coronary syndrome (ACS‐CS) who require short‐term mechanical circulatory support ...(ST‐MCS).
Background
ACS‐CS mortality is high. ST‐MCS is an attractive treatment option for hemodynamic support and stabilization of deteriorating patients. Mortality prediction modeling for ACS‐CS patients requiring ST‐MCS has not been well‐defined.
Methods
The Utah Cardiac Recovery (UCAR) Shock database was used to identify patients admitted with ACS‐CS requiring ST‐MCS devices between May 2008 and August 2018. Pre‐ST‐MCS clinical, laboratory, echocardiographic, and angiographic data were collected. The primary endpoint was 30‐day all‐cause mortality. A weighted score comprising of pre‐ST‐MCS variables independently associated with 30‐day all‐cause mortality was derived and internally validated.
Results
A total of 159 patients (mean age, 61 years; 78% male) were included. Thirty‐day all‐cause mortality was 49%. Multivariable analysis resulted in four independent predictors of 30‐day all‐cause mortality: age, lactate, SCAI CS classification, and acute kidney injury. The model had good calibration and discrimination (area under the receiver operating characteristics curve 0.80). A predictive score (ranging 0–4) comprised of age ≥ 60 years, pre‐ST‐MCS lactate ≥2.5 mmol/L, AKI at time of ST‐MCS implementation, and SCAI CS stage E effectively risk stratified our patient population.
Conclusion
The ACS‐MCS score is a simple and practical predictive score to risk‐stratify CS secondary to ACS patients based on their mortality risk. Effective mortality risk assessment for ACS‐CS patients could have implications on patient selection for available therapeutic strategy options.
Angioedema is a rare, potentially life-threatening adverse event of renin–angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized ...clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients ≥100 and a duration of ≥8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval CI 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.
Endomyocardial biopsy (EMB), the reference surveillance test for acute rejection (AR) in heart transplant (HTx) recipients, is invasive, costly, and shows significant interobserver variability. ...Recent studies indicate that donor-derived cell-free DNA (dd-cfDNA), obtained non-invasively from blood, is associated with AR and could reduce the frequency of EMB surveillance. The aim of this study was to examine the performance characteristics of a novel test for detecting AR in adult HTx recipients.
Plasma samples with contemporaneous EMBs were obtained from HTx recipients. A clinically available SNP-based massively multiplexed-PCR dd-cfDNA assay was used to measure dd-cfDNA fraction. dd-cfDNA fractions were compared with EMB-defined rejection status and test performance was assessed by constructing ROC curves and calculating accuracy measures.
A total of 811 samples from 223 patients with dd-cfDNA testing and contemporaneous EMB were eligible for the study. dd-cfDNA fraction was significantly higher in AR (median 0.58%, IQR, 0.13%-1.68%) compared to non-AR (median 0.04%, IQR, 0.01%-0.11%, pc < 0.001). ROC analysis produced an area under the curve (AUC-ROC) of 0.86 (95% CI, 0.77-0.96). Defining samples with dd-cfDNA fraction ≥0.15% as AR yielded 78.5% sensitivity (95% CI, 60.7%-96.3%) and 76.9% specificity (95% CI, 71.1%-82.7%). Positive and negative predictive values were 25.1% (95% CI, 18.8%-31.5%) and 97.3% (95% CI, 95.1%-99.5%) respectively, calculated using the cohort AR prevalence of 9.0% (95% CI, 5.3%-12.8%) with adjustment for repeat samples.
This novel dd-cfDNA test detects AR in HTx recipients with good accuracy and holds promise as a noninvasive test for AR in HTx recipients.
Aims
Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous‐flow left ventricular assist device ...(LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS.
Methods and results
Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta‐blocker, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end‐organ injury, or neurological events. In patients with high baseline pre‐LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis.
Conclusions
Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD‐induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post‐LVAD adverse events during the follow‐up period.
Abstract Background Peripheral edema is a common adverse effect of calcium channel blockers. The addition of a renin-angiotensin system blocker, either an angiotensin-converting enzyme inhibitor or ...an ARB, has been shown to reduce peripheral edema in a dose-dependent way. Methods We performed a MEDLINE/COCHRANE search for all prospective randomized controlled trials in patients with hypertension, comparing calcium channel blocker monotherapy with calcium channel blocker/renin-angiotensin system blocker combination from 1980 to the present. Trials reporting the incidence of peripheral edema or withdrawal of patients because of edema and total sample size more than 100 were included in this analysis. Results We analyzed 25 randomized controlled trials with 17,206 patients (mean age 56 years, 55% were men) and a mean duration of 9.2 weeks. The incidence of peripheral edema with calcium channel blocker/renin-angiotensin system blocker combination was 38% lower than that with calcium channel blocker monotherapy ( P < .00001) (relative risk RR 0.62; 95% confidence interval CI, 0.53-0.74). Similarly, the risk of withdrawal due to peripheral edema was 62% lower with calcium channel blocker/renin-angiotensin system blocker combination compared with calcium channel blocker monotherapy ( P = .002) (RR 0.38; 95% CI, 0.22-0.66). ACE inhibitors were significantly more efficacious than ARBs in reducing the incidence of peripheral edema ( P < .0001) (ratio of RR 0.74; 95% CI, 0.64-0.84) (indirect comparison). Conclusion In patients with hypertension, the calcium channel blocker/renin-angiotensin system blocker combination reduces the risk of calcium channel blocker-associated peripheral edema when compared with calcium channel blocker monotherapy. ACE inhibitor seems to be more efficacious than ARB in reducing calcium channel blocker-associated peripheral edema, but head-to-head comparison studies are needed to prove this.
Mechanical circulatory support (MCS) leads to favorable changes in the failing heart at the molecular, cellular, and structural levels. However, myocardial recovery leading to device explantation is ...rare. We reasoned that the multicenter United Network for Organ Sharing (UNOS) registry might provide insights into clinical predictors and outcomes of the recovery process.
The MCS device data set of the UNOS registry was queried for patients with long-term continuous-flow left ventricular assist devices (CF-LVADs) that were explanted for heart transplantation or indication of recovery. Analysis was restricted to adult patients (≥18 years old) who were listed for an initial heart transplantation. Patients with CF-LVADs that were explanted because of recovery were compared with patients with CF-LVADs who underwent transplantation.
We identified 594 patients with HeartMate II devices and 92 patients with HeartWare devices. Duration of support was on average 500.4 ± 325.3 days. In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery. Univariate predictors of recovery in patients with long-term LVADs included younger age (40 years vs 53 years), female sex, lower body mass index (25.7 kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation period, freedom from death or transplantation was 66% at 1 year.
The incidence of recovery on device support is low in the current MCS era and limited to a select cohort of predominantly young patients with non-ischemic myopathy. Given the high incidence of disease recurrence, patients should be closely followed after device explantation.
The twelfth annual report from The Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) highlights outcomes for 26 688 continuous-flow ...left ventricular assist device (LVAD) patients over the past decade (2011-2020). In 2020, we observed the largest drop in yearly LVAD implant volumes since the registry’s inception, which reflects the effects of the COVID-19 pandemic on cardiac surgical volumes in the United States. The 2018 heart transplant allocation policy change in the United States continues to affect LVAD implantation volumes and device strategy, with 78.1% of patients now receiving LVAD implants as destination therapy. Despite an older and sicker patient cohort, survival in the recent era (2016-2020) at 1 and 2 years continues to improve at 82.8% and 74.1%. Patient adverse event profile has also improved in the recent era, with significant reductions in stroke, gastrointestinal bleeding, infection, and device malfunction/pump thrombosis. Finally, we review the burden of readmissions after LVAD implant and highlight an opportunity to improve patient outcomes by reducing this frequent and vexing problem.
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