Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.

BACKGROUND: The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined. OBJECTIVES: The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression. RESULTS: The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m2 decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (Pinteraction = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months. CONCLUSIONS: In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).

Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Outcomes in Left Ventricular Assist Device Patients with Aortic Insufficiency.

Background: Worsening aortic insufficiency (AI) is a known sequela of prolonged continuous-flow left ventricular assist device (LVAD) support with a significant impact on patient outcomes. While medical treatment may relieve symptoms, it is unlikely to halt progression. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are among non-medical interventions available to address post-LVAD AI. Limited data are available on outcomes with either SAVR or TAVR for the management of post-LVAD AI. Methods: The National Inpatient Sample data collected for hospital admissions between the years 2015 and 2018 for patients with pre-existing continuous-flow LVAD undergoing TAVR or SAVR for AI were queried. The primary outcome of interest was a composite of in-hospital mortality, stroke, transient ischaemic attack, MI, pacemaker implantation, need for open aortic valve surgery, vascular complications and cardiac tamponade. Results: Patients undergoing TAVR were more likely to receive their procedure during an elective admission (57.1 versus 30%, p=0.002), and a significantly higher prevalence of comorbidities, as assessed by the Elixhauser Comorbidity Index, was observed in the SAVR group (29 versus 18; p=0.0001). We observed a significantly higher prevalence of the primary composite outcome in patients undergoing SAVR (30%) compared with TAVR (14.3%; p=0.001). Upon multivariable analysis adjusting for the type of admission and Elixhauser Comorbidity Index, TAVR was associated with significantly lower odds of the composite outcome (odds ratio 0.243; 95% CI [0.06-0.97]; p=0.045). Conclusion: In this nationally representative cohort of LVAD patients with post-implant AI, it was observed that TAVR was associated with a lower risk of adverse short-term outcomes compared with SAVR.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

HeartMate 3 in a ccTGA patient.

A 49-year-old female with congenitally corrected (or levo-) transposition of the great arteries complicated by nonischemic cardiomyopathy presented for worsening heart failure despite guideline-directed medical therapy and was found to be in cardiogenic shock. She successfully underwent ventricular assist device placement with a HeartMate III to her systemic right ventricle as a bridge to transplantation.

An Incidentally Discovered Pedunculated Degenerative Cyst on the Aortic Valve.

We report the case of a pedunculated cystic mass on the aortic valve discovered in a patient presenting for a routine echocardiogram. The highly mobile nature of the mass warranted prompt surgical removal to prevent cardioembolic complications. The mass was preoperatively thought to be a papillary fibroelastoma. However, the patient's history, mass morphology, and histopathology pointed toward a simple degenerative cyst--previously unreported on the aortic valve. This report describes this rare finding, discusses relevant differential diagnoses, and underscores the importance of surgical intervention in such cases.

Association of cystatin C with measures of obesity and its impact on cardiovascular events among healthy US adults.

BACKGROUND: This study sought to explore the relationship between cystatin C (CysC) and anthropometric measures of obesity and the influence of this association on mortality [cardiovascular disease (CVD), coronary heart disease, and all-cause] in a nationally representative population free of CVD, diabetes mellitus, and macroalbuminuria (MA). METHODS: The study cohort included 4577 adult participants of the Third National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to ascertain the association between various anthropometric measures and CysC. Formal statistical analyses of the interaction term between anthropometric measures and CysC for outcomes were performed followed by stratified multivariate Cox proportional hazard analyses. RESULTS: A moderate degree of association was seen between CysC and measures of visceral adiposity as represented by waist-to-height ratio (WHR) and waist circumference (WC) and only a weak association between CysC and body mass index (BMI). CysC was predictive of all study outcomes in individuals with normal anthropometric measurements only. CONCLUSIONS: CysC correlated better with measures of visceral adiposity (WC and WHR) compared to BMI and appears to be a better predictor of adverse cardiovascular outcomes among those with anthropometric measures not suggestive of obesity compared to those with abnormal measures of anthropometry.

Non-high-density lipoprotein cholesterol and coronary artery calcium progression in a multiethnic US population.

Non-high-density lipoprotein cholesterol (non-HDLc) is an independent predictor of cardiovascular disease risk, with elevated levels signifying an increased risk beyond low-density lipoprotein. Previous data have shown inconsistent association of lipid subfractions with progression of coronary artery calcium (CAC), a surrogate marker of incident cardiovascular disease. We sought to evaluate the association between non-HDLc and development (incident) and progression of CAC in a cohort of multiethnic asymptomatic subjects. The cohort (n = 5,705) was derived from the limited access data set of the Multi-Ethnic Study of Atherosclerosis obtained from the National Heart Lung and Blood Institute. Multivariable regression analysis was performed to derive the association between non-HDLc and incident CAC (n = 2,927) and non-HDLc and progression of CAC (n = 2,778). In the population without CAC at baseline, non-HDLc, especially >190 mg/dl, was independently associated with incident CAC (relative risk 1.40, 95% confidence interval 1.09 to 1.79, p = 0.008) after adjustments with age, gender, race, systolic blood pressure, antihypertension medication use, smoking, diabetes, lipid-lowering therapy use, follow-up duration, and waist-hip ratio. Similarly, among those with CAC at baseline, non-HDLc levels >190 mg/dl were associated with significant CAC progression in the overall population (ß 16.4, 95% confidence interval -5.63 to 27.2, p = 0.003) after adjustments. In conclusion, non-HDLc levels, especially >190 mg/dl, are consistently associated with increased risk of CAC progression. Our results suggest that among lipid fractions, non-HDLc may be best suited for the prediction of future CAC progression.

Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population: findings from the 1999-2004 NHANES.

BACKGROUND: Red cell distribution width (RDW) has been shown to predict all-cause and cardiovascular (CVD) mortality. However, the predictive ability of RDW for future coronary heart disease (CHD) mortality in comparison to high sensitivity C-reactive protein (hs-CRP) has not been assessed in a population cohort free of CVD. METHODS: Analysis was performed on 8,513 adult participants (age > 20 years) free of CVD from the National Health and Nutrition Examination Surveys 1999-2004. Cox-proportional hazard analyses were used to assess the role of RDW and hs-CRP in CHD mortality and in subgroups based on high and low RDW and hs-CRP. RESULTS: On adjustment for traditional risk factors (age, sex, systolic blood pressure, anti-hypertensive medication use, total cholesterol, high density lipoprotein cholesterol, lipid lowering therapy, smoking, diabetes mellitus, anemia, mean corpuscular volume and nutritional deficiencies), RDW [hazard ratio (HR) 1.26 95% Confidence Interval (CI) [1.12-1.42] p < 0.001] remained an independent predictor, while hs-CRP [HR 1.18 95% CI [0.98-1.41] p = 0.077] did not. On comparative analysis, high RDW (> 12.6%) was predictive of CHD mortality irrespective of hs-CRP status [hs-CRP ≤ 3 mg/L (HR 1.17 95% CI [1.01-1.36] p = 0.031)] and hs-CRP > 3 mg/L (HR 1.44 95% CI [1.23-1.68] p < 0.001). Hs-CRP was not predictive in either high or low RDW subgroup. CONCLUSION: RDW but not hs-CRP was associated with CHD mortality independent of traditional risk factors in a cohort with no pre-existing CVD. RDW may be considered a stronger biomarker for CHD death than hs-CRP and needs further prospective evaluation in CVD risk assessment.

Association between arterial elasticity indices and coronary artery calcium in a healthy multi-ethnic cohort.

OBJECTIVES: Reduced arterial elasticity is a risk factor for coronary artery disease. Our main objective was to evaluate the association between large arterial elasticity (LAE) and small arterial elasticity (SAE) with subclinical atherosclerosis as reflected by the coronary artery calcium score (CACS). METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) includes a multi-ethnic, population-based cohort (n = 6,814), aged 45-84 years, free from clinical cardiovascular disease. We undertook a post hoc analysis of the NHLBI limited access data set of MESA subjects (n = 6,278) to evaluate the association between LAE and SAE with CACS [divided in to 4 categories: none (reference), 1-99, 100-299, and ≥ 300] using multivariable adjusted logistic regression analysis. RESULTS: After adjustments for age, sex, systolic blood pressure, anti-hypertensive medications use, race, smoking, diabetes, high-density lipoprotein and total cholesterol, and high-sensitivity C-reactive protein, both LAE [adjusted odds ratio (aOR) 0.65; 95% CI 0.49-0.87 for CACS ≥ 300] and SAE (aOR 0.68, 95% CI 0.56-0.83 for CACS ≥ 300) were significantly (p < 0.001 for both) associated with a higher CACS. CONCLUSION: Both LAE and SAE, independent of traditional risk factors and inflammation, are associated with subclinical coronary atherosclerosis.

Red cell distribution width and risk of peripheral artery disease: analysis of National Health and Nutrition Examination Survey 1999-2004.

Red cell distribution width (RDW) is an independent predictor of the 10-year estimated risk of coronary heart disease (CHD) events. However, RDW's association with peripheral artery disease (PAD) - a CHD risk equivalent - has not been evaluated to date. In this cross-sectional study, we examined 6950 participants of the National Health and Nutrition Examination Survey, 1999-2004. PAD was defined as an ankle-brachial index below 0.9 (n = 618). RDW was divided into quartiles (Q) (Q1: ≤ 12.2; Q2: 12.3-12.5; Q3: 12.6-13.0; Q4: ≥ 13.1) and PAD risk was compared across these quartiles using adjusted multivariate logistic regression. A graded increase in prevalent PAD with increasing RDW quartiles was observed (4.2% in Q1 vs 13.9% in Q4; test of trend p < 0.001). Risk of PAD was significantly higher (odds ratio (OR) 1.19, 95% confidence interval (CI): 1.06-1.34; p = 0.003) after adjusting for age, sex, race, body mass index, hypertension, hyperlipidemia, diabetes, smoking, estimated glomerular filtration rate, C-reactive protein, hemoglobin, mean corpuscular volume, and nutritional factors (folate, iron and vitamin B(12)) deficiencies with each unit (0.1) increase in RDW. Upon receiver-operating characteristics analysis, the predictive accuracy of the American College of Cardiology / American Heart Association (ACC/AHA)-defined PAD screening criteria (for a high-risk population) was 0.657 at best, but improved significantly (0.727) after addition of RDW (p < 0.0001). In conclusion, higher levels of RDW are independently associated with a higher risk of PAD and can significantly improve the risk prediction beyond that estimated by ACC/AHA-defined PAD screening criteria.

Gender and ethnic differences in red cell distribution width and its association with mortality among low risk healthy United state adults.

Limited information is available about gender and ethnic differences in red cell distribution width (RCDW) with regard to its relation to mortality in a population free of cardiovascular (CV) disease and diabetes. To assess gender and ethnic differences in RCDW and their effect on the association between RCDW and mortality, the Third National Health and Nutritional Examination Survey (n = 15,460, 1988 to 1994) data were examined. Multivariate adjusted Cox proportional hazard analysis was performed to assess effect of gender and ethnicity on the association between RCDW and mortality (total, CV disease, and coronary heart disease [CHD]). RCDW (mean ± SE) was greater in black women (13.1 ± 0.03) and men (13.4 ± 0.02) compared to women of white (12.9 ± 0.02) and other (13.0 ± 0.07) ethnicities and men of white (13.3 ± 0.02) and other (13.3 ± 0.07) ethnicities, respectively (p <0.001). The interaction between RCDW and gender was statistically significant for all study outcomes (p <0.001) but nonsignificant for RCDW and ethnicity. After adjusting for key variables, RCDW in women was associated with adjusted hazard ratios of 1.22 (95% confidence interval [CI] 1.14 to 1.31) for all-cause mortality, 1.17 (95% CI 1.07 to 1.28) for CV deaths, and 1.18 (95% CI 1.03 to 1.35) for CHD deaths; in men, adjusted hazard ratios were 1.29 (95% CI 1.20 to 1.38) for all-cause mortality, 1.27 (95% CI 1.17 to 1.37) for CV deaths, and 1.25 (95% CI 1.13 to 1.39) for CHD deaths (p <0.05 for all). In conclusion, blacks and men have significantly greater RCDWs compared to whites and women. Greater RCDW is associated with a greater risk of mortality in men compared to women, whereas no effect modification is observed by ethnicity.

Relationship between red cell distribution width and microalbuminuria: a population-based study of multiethnic representative US adults.

INTRODUCTION: Microalbuminuria (MA), a renal marker of vascular injury, is an independent predictor of cardiovascular (CV) events. Red cell distribution width (RDW), an emerging CV risk predictor, has not been evaluated for its association with MA. METHODS: We evaluated 8,499 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2006, where RDW was evaluated as a continuous variable and in quartiles (Q(1) ≤ 12.1, Q(2) 12.2-12.5, Q(3) 12.6-13 and Q(4) >13). Multivariate adjusted logistic regression analysis was performed to estimate the odds of having MA (n = 1,736; adjusted for traditional CV risk factors, race, BMI, estimated glomerular filtration rate, hemoglobin, mean corpuscular volume, high-sensitivity C-reactive protein and nutritional factors deficiencies of iron, folate and vitamin B(12)). RESULTS: The prevalence of MA increased with increasing RDW (13.52% in Q(1) vs. 30.02% in Q(4), p < 0.001). The odds of having MA for those in Q(4) was 2.49 (95% CI: 1.95-3.18, p < 0.001) compared to those in Q(1) after the adjustments. No effect modification was observed by covariates on the association between RDW and MA. CONCLUSION: Elevated RDW is independently associated with a higher risk of MA. An interaction between chronic inflammation, oxidative stress, neurohumoral overactivity and endothelial dysfunction may explain this association and the attendant elevated CV/renal risk.

Role of irbesartan in prevention of post-coronary artery bypass graft atrial fibrillation.

BACKGROUND AND OBJECTIVE: Atrial fibrillation (AF) is a common complication of cardiothoracic surgery (CTS). Existing evidence about the potential protective role of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) for post-CTS AF has been limited and conflicting. In this single-blind, open-label, randomized prospective pilot study, we evaluated the potential protective role of irbesartan (an ARB) in post-coronary artery bypass graft (CABG) AF. METHODS: A total of 100 consecutive patients undergoing CABG were randomly assigned to irbesartan (n = 50) versus no irbesartan (n = 50) for 5 days prior to the scheduled surgery. Data were collected for imaging studies, laboratory values, and peri-operative details. Patients were monitored post-operatively for in-hospital AF episodes. Unadjusted and adjusted logistic regression analysis was performed to assess the effect of irbesartan on the incidence of post-CABG AF. RESULTS: A total of 14 patients developed AF during their post-operative hospital stay. The incidence of AF in patients who received irbesartan was 6% (n = 3) compared with 22% (n = 11) in patients who did not receive irbesartan (p = 0.021). Univariate logistic regression analysis identified irbesartan and age as statistically significant variables. An adjusted multivariate logistic model identified irbesartan as an important protective factor against development of post-CABG AF (adjusted odds ratio [OR] 0.20; 95% confidence interval [CI] 0.04, 0.94; p = 0.04). Increasing age (adjusted OR 1.09, 95% CI 1.01, 1.17; p = 0.03) was also identified as an independent risk factor for development of post-CABG AF. CONCLUSION: Pretreatment with irbesartan tends to have a significant protective effect against the occurrence of AF during the post-operative period in patients undergoing CABG.

Glycosylated hemoglobin and prevalent metabolic syndrome in nondiabetic multiethnic U.S. adults.

BACKGROUND: Metabolic syndrome poses a significant risk for cardiovascular disease. Recently, glycosylated hemoglobin (HbA1c) has been included in the diagnostic criteria for diabetes mellitus and prediabetes. We sought to determine if HbA1c is associated with prevalent metabolic syndrome in nondiabetic U.S. adults. METHODS: A total of 9,022 nondiabetic participants of National Health and Nutrition Examination Surveys 1999-2008 (age, 47.5 ± 18.3 years, 51% females) were divided into quintiles (Q) of HbA1c: Q1 (reference), ≤5%; Q2, 5.1%-5.3%; Q3, 5.4%-5.5%; Q4, 5.6%-5.7%; and Q5, ≥5.8%. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify metabolic syndrome (n=2,821; 31.3%). Unadjusted and adjusted multivariate logistic regression analysis was performed to assess the risk of metabolic syndrome. RESULTS: A graded increase in odds of having prevalent metabolic syndrome with increase from each quintile of HbA1c compared to Q1 was observed after adjusting for age, sex, race, body mass index (BMI), total cholesterol, lipid-lowering therapy, current smoking, family history of diabetes, C-reactive protein, and fasting insulin. Stratified analysis based on gender, ethnicity, and BMI showed similar results. The HbA1c value of ≥5.4% remained appropriate cutoff for predicting metabolic syndrome in Caucasians and Hispanics, whereas ≥5.6% provided the best accuracy for African Americans based on receiver operating characteristics analysis. CONCLUSION: HbA1c much below the level for prediabetes was associated with prevalence of the metabolic syndrome in a cohort of nondiabetic U.S. adults. HbA1c can be considered as a surrogate marker for metabolic syndrome in nondiabetics.

Unique case of presumed lisinopril-induced hepatotoxicity.

PURPOSE: A case of presumed lisinopril-induced hepatotoxicity is reported. SUMMARY: A 30-year-old woman had complained of fatigue and yellow eyes for two days. Her medical history included hypertension and nephrotic syndrome. Her medications included furosemide 20 mg daily (for almost 6.5 years) and lisinopril 10 mg daily (for eight months). She had been treated with quinapril, enalapril, and lisinopril in the past by different primary care physicians without any adverse effects. She did not abuse alcohol and denied any liver-related problems in the past. Her physical examination revealed icterus and right-upper-quadrant abdominal tenderness. Initial laboratory tests revealed elevated liver enzyme values. Ultrasonography and computed tomography (CT) scans of the patient's abdomen suggested hepatocellular disease with mild hepatomegaly and a normal biliary tract. Due to worsening bilirubin and liver enzyme values, lisinopril was stopped. In the absence of a probable cause of the patient's hepatotoxicity, a CT-guided liver biopsy was performed. Histological examination of the liver tissue showed moderate chronic inflammatory cell infiltrates in the portal area, predominantly composed of lymphocytes with mild-to-moderate interface hepatitis. No centrolobular necrosis or steatosis was seen. After lisinopril was discontinued, there was a rapid improvement in the patient's clinical and biochemical pictures. On her follow-up clinic visit approximately two months later, all of her liver enzyme values had normalized. CONCLUSION: A woman who had received quinapril, enalapril, and lisinopril in the past without apparent adverse effects developed hepatocellular disease that became evident eight months after lisinopril therapy was reinstituted. The presumed hepatotoxicity resolved after discontinuation of lisinopril.