Farid Foroutan

Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline

In patients with symptomatic severe aortic stenosis but at lower risk of perioperative death, how do minimally invasive techniques compare with open surgery? Prompted by a recent trial, an expert panel produced these recommendations based on three linked rapid systematic reviews

Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies

Objective To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. Design Systematic review and meta-analysis of observational studies. Data sources Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. Study selection Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. Methods Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. Results In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). Conclusion Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.

Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes

BACKGROUND One major disadvantage of ventricular assist device (VAD) therapy is the development of human-leukocyte antigen (HLA) antibodies. We aimed to identify factors associated with HLA antibodies during continuous flow (CF)-VAD support and assess the effect on transplant probability and outcomes. METHODS We included 143 consecutive heart failure patients who received a CF-VAD as a bridge-to-transplant at 3 institutions. Factors associated with post-VAD peak panel reactive antibodies (PRA) among several measurements were identified using multivariable linear regression. A parametric survival model was used to assess transplant waiting time and probability, risk of rejection, and a composite outcome of rejection, graft failure, and death. RESULTS Thirty-six patients (25%) were female; mean age was 47 ± 13 years. Eighty-one patients (57%) had a pre-VAD PRA of 0%, and 16 were highly sensitized (PRA > 80%). Age, female sex, and pre-VAD PRA were independently associated with post-VAD PRA. A 10-year increase in age was associated with a 5% decrease in post-VAD PRA (p = 0.03). Post-VAD PRA was 19% higher in women vs men (p < 0.01). A 10%-increase in pre-VAD PRA was associated with a 4.7% higher post-VAD PRA (p < 0.01). During a mean follow-up of 12 ± 11 months, 90 patients underwent cardiac transplantation. A 20% increase in post-VAD PRA was associated with 13% lower probability of transplant (hazard ratio, 0.87; 95% confidence interval, 0.76-0.99). A high PRA was not associated with adverse post-transplant outcomes. CONCLUSIONS Younger age, female sex, and pre-VAD PRA were independent predictors of elevated PRA post-VAD. Higher PRA was significantly associated with lower transplant probability but not increased rejection, graft failure, or death after transplant.

Cerebral Embolic Protection Devices During Transcatheter Aortic Valve Implantation

Background and Purpose— Silent ischemic embolic lesions are common after transcatheter aortic valve implantation (TAVI). The use of embolic protection devices (EPD) may reduce the occurrence of these embolic lesions. Thus, a quantitative overview and credibility assessment of the literature was necessary to draw a robust message about EPD. Therefore, the aim of this meta-analysis was to study whether the use of EPD reduces silent ischemic and clinically evident cerebrovascular events associated with TAVI. Methods— We conducted a comprehensive search to identify studies that evaluated patients undergoing TAVI with or without EPD. Random-effects meta-analyses were performed to estimate the effect of EPD compared with no-EPD during TAVI using aggregate data. Results— Sixteen studies involving 1170 patients (865/305 with/without EPD) fulfilled the inclusion criteria. The EPD delivery success rate was reported in all studies and was achieved in 94.5% of patients. Meta-analyses evaluating EPD versus without EPD strategies could not confirm or exclude any differences in terms of clinically evident stroke (relative risk, 0.70; 95% confidence interval [CI], 0.38–1.29; P=0.26) or 30-day mortality (relative risk, 0.58; 95% CI, 0.20–1.64; P=0.30). There were no significant differences in new-single, multiple, or total number of lesions. The use of EPD was associated with a significantly smaller ischemic volume per lesion (standardized mean difference, −0.52; 95% CI, −0.85 to −0.20; P=0.002) and smaller total volume of lesions (standardized mean difference, −0.23; 95% CI, −0.42 to −0.03; P=0.02). Subgroup analysis by type of valve showed an overall trend toward significant reduction in new lesions per patient using EPD (standardized mean difference, −0.41; 95% CI, −0.82 to 0.00; P=0.05), driven by self-expanding devices. Conclusions— The use of EPD during TAVI may be associated with smaller volume of silent ischemic lesions and smaller total volume of silent ischemic lesions. However, EPD may not reduce the number of new-single, multiple, or total number of lesions. There was only very low quality of evidence showing no significant differences between patients undergoing TAVI with or without EPD with respect to clinically evident stroke and mortality.

Outcomes in adult congenital heart disease patients undergoing heart transplantation: A systematic review and meta-analysis

BACKGROUND Studies assessing mortality and morbidity in adult transplant recipients with congenital heart disease (CHD) are limited. We conducted a systematic review and meta-analysis comparing post-transplant outcomes in these 2 populations. METHODS After conducting an electronic database search, we selected studies evaluating mortality, cause-specific mortality, and risk of reoperation and dialysis in adult CHD vs non-CHD patients. We used random-effects models for the meta-analysis. RESULTS Thirty-day mortality was significantly higher in CHD vs non-CHD patients (risk ratio [RR], 2.18; 95% confidence interval [CI], 1.62-2.93; I2 = 41%). This was influenced by increased mortality in Fontan/Glenn patients compared with non-CHD patients (RR, 3.3; 95% CI, 1.89-5.77; I2 = 0%). Mortality at 1 and 5 years was higher in the CHD population, although neither achieved statistical significance. Ten-year mortality was significantly lower in CHD patients (RR, 0.75; 95% CI, 0.60-0.95, I2 = 42%). Deaths caused by malignancy, infection, rejection, and cardiac allograft vasculopathy were decreased in CHD patients, although only death from malignancy achieved significance. Death secondary to primary graft failure, stroke, and hemorrhage was significantly higher in CHD patients. Risk of reoperation and dialysis were not statistically different between the 2 groups. CONCLUSIONS Although adult CHD patients have higher early mortality, post-transplantation long-term survival is superior to non-CHD recipients. The challenge is to identify the CHD patients who will benefit from transplantation vs those who are higher risk.

Structural valve deterioration after transcatheter aortic valve implantation

Background Transcatheter aortic valve implantation (TAVI), widely used to treat high-risk patients with severe symptomatic aortic stenosis, has recently been extended to younger patients at lower operative risk in whom long-term durability of TAVI devices is an important concern. Therefore, we conducted a systematic review and meta-analysis of observational studies addressing the frequency of structural valve deterioration (SVD) after TAVI. Methods We searched Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to September 2016. We included observational studies following patients with TAVI for at least 2 years. Independently and in duplicate, we evaluated study eligibility, extracted data, and assessed risk of bias for SVD post-TAVI. Our review used the GRADE system to assess quality of evidence. We pooled incidence rates using a random effects model. Results Thirteen studies including 8914 patients, with a median follow-up between 1.6 and 5 years, reported an incidence of SVD post-TAVI between 0 to 1.34 per 100 patient years. The pooled incidence of SVD was 28.08 per 10 000 patients/year (95% CI 2.46 to 73.44 per 100 patient years). Of those who developed SVD, 12% underwent valve re-intervention. Confidence in the evidence was moderate due to inconsistency among studies. Conclusion Structural valve deterioration is probably an infrequent event within the first 5 years after TAVI. Ascertaining the impact of SVD and the need for valve-related re-interventions to inform recommendations for patients with a longer life-expectancy will require studies including a large number of patients with longer follow-up (>10 years).

Application of minimal important differences in degenerative knee disease outcomes: a systematic review and case study to inform BMJ Rapid Recommendations

Objectives To identify the most credible anchor-based minimal important differences (MIDs) for patient important outcomes in patients with degenerative knee disease, and to inform BMJ Rapid Recommendations for arthroscopic surgery versus conservative management Design Systematic review. Outcome measures Estimates of anchor-based MIDs, and their credibility, for knee symptoms and health-related quality of life (HRQoL). Data sources MEDLINE, EMBASE and PsycINFO. Eligibility criteria We included original studies documenting the development of anchor-based MIDs for patient-reported outcomes (PROs) reported in randomised controlled trials included in the linked systematic review and meta-analysis and judged by the parallel BMJ Rapid Recommendations panel as critically important for informing their recommendation: measures of pain, function and HRQoL. Results 13 studies reported 95 empirically estimated anchor-based MIDs for 8 PRO instruments and/or their subdomains that measure knee pain, function or HRQoL. All studies used a transition rating (global rating of change) as the anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found wide variation in MID values. Many studies suffered from serious methodological limitations. We identified the following most credible MIDs: Western Ontario and McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15). Conclusions We were able to distinguish between more and less credible MID estimates and provide best estimates for key instruments that informed evidence presentation in the associated systematic review and judgements made by the Rapid Recommendation panel. Trial registration number CRD42016047912.

Diastolic Pressure Difference to Classify Pulmonary Hypertension in the Assessment of Heart Transplant Candidates

Background: The diastolic pressure difference (DPD) is recommended to differentiate between isolated postcapillary and combined pre-/postcapillary pulmonary hypertension (Cpc-PH) in left heart disease (PH-LHD). However, in usual practice, negative DPD values are commonly calculated, potentially related to the use of mean pulmonary artery wedge pressure (PAWP). We used the ECG to gate late-diastolic PAWP measurements. We examined the method’s impact on calculated DPD, PH-LHD subclassification, hemodynamic profiles, and mortality. Methods and Results: We studied patients with advanced heart failure undergoing right heart catheterization to assess cardiac transplantation candidacy (N=141). Pressure tracings were analyzed offline over 8 to 10 beat intervals. Diastolic pulmonary artery pressure and mean PAWP were measured to calculate the DPD as per usual practice (diastolic pulmonary artery pressure–mean PAWP). Within the same intervals, PAWP was measured gated to the ECG QRS complex to calculate the QRS-gated DPD (diastolic pulmonary artery pressure–QRS-gated PAWP). Outcomes occurring within 1 year were collected retrospectively from chart review. Overall, 72 of 141 cases demonstrated PH-LHD. Within PH-LHD, the QRS-gated DPD yielded higher calculated DPD values (3 [−1 to 6] versus 0 [−4 to 3] mm Hg; P<0.01) and a greater proportion of Cpc-PH (24% versus 8%; P<0.01) versus the usual practice DPD. Cases reclassified as Cpc-PH based on QRS-gated DPD demonstrated higher pulmonary arterial pressures versus isolated postcapillary pulmonary hypertension (P<0.05). One-year mortality was similar between PH-LHD groups. Conclusions: The DPD calculated in usual practice is underestimated in PH-LHD, which may classify Cpc-PH patients as isolated postcapillary pulmonary hypertension. The QRS-gated DPD reclassifies a subset of PH-LHD patients from isolated postcapillary pulmonary hypertension to Cpc-PH, which is characterized by an adverse hemodynamic profile.

Tricuspid Valve Annular Dilation as a Predictor of Right Ventricular Failure After Implantation of a Left Ventricular Assist Device.

Tricuspid annular (TA) dilation has been suggested as a more reliable marker of concomitant advanced right ventricular failure (RVF) than severity of tricuspid regurgitation (TR). Our objective was to examine the impact of TA dilation on occurrence of RVF and in‐hospital mortality following left ventricular assist device (LVAD) implant.

The prognostic significance of frailty compared to peak oxygen consumption and B-type natriuretic peptide in patients with advanced heart failure

Frailty assessment has become an integral part of the evaluation of potential candidates for heart transplantation and ventricular assist device (HTx/VAD). The impact of frailty, as a heart failure risk factor or to identify those who will derive the greatest benefit with HTx/VAD remains unclear. The aim of this study was to evaluate the independent prognostic relevance of frailty assessment from peak oxygen consumption (peak VO2) or B‐type natriuretic peptide (BNP) on mortality in patients referred for advanced heart failure therapies. Frailty was measured using modified Fried frailty criteria. In 201 consecutive patients, during a median follow‐up of 17.5 months (IQR 11‐29.2), there were 25 (12.4%) deaths. One‐year survival was 100%, 94%, and 78% in nonfrail, prefrail, and frail patients, respectively (log rank P = .0001). Frailty was associated with a twofold increase risk of death (HR 2.01, P < .0001, 95% CI 1.42‐2.84). When adjusted for BNP or peak VO2, frailty was not associated with a significant risk of all‐cause death. However, when peak VO2 is stratified into two categories (≥12 mL/kg/min vs <12 mL/kg/min), frailty was associated with increased mortality in patients with a lower peak VO2 (HR 1.72, P = .006).