Briasoulis, Alexandros

Abstract Aims Early studies from the 1990s have shown that statins improve survival and attenuate cardiac allograft vasculopathy (CAV). However, little contemporary data are available on the incremental benefit of statins with the current use of new-generation immunosuppressive agents and the use of coronary intravascular ultrasound for assessment of CAV. We sought to investigate the effect of early statin (ES) as compared with late statin (LS) initiation after heart transplantation (HT) on long-term CAV progression and clinical outcomes in a large contemporary HT cohort. Methods and results We analysed a cohort of 409 adult HT recipients. CAV progression was assessed by serial coronary intravascular ultrasound volumetric measurements of the differences between baseline and last follow-up plaque volume (PV) and plaque index (PV/vessel volume ratio). CAV progression and clinical outcomes were compared between the ES (<2 years after HT) and the LS (>2 years after HT) groups. During a median follow-up of 8.2 years, ES resulted in significantly lower change (Δ) of plaque index (+3.8% ± 1.7% vs. +8.2% ± 3.6%; P = 0.0008) and PV (+0.8 ± 0.3 vs. +1.9 ± 1.2; P = 0.045) compared with LS group. In a Cox proportional hazards regression model and after adjustment for baseline characteristics, ES was associated with a 52% decreased risk of CAV-associated events (hazard ratio 0.48, 95% confidence interval: 0.27–0.91; P = 0.025) and a 42% decreased risk of the composite endpoint of all-cause mortality and CAV-associated events (hazard ratio 0.58, 95% confidence interval: 0.38–0.91; P = 0.019). Conclusions Early initiation of statin therapy after HT results in attenuated CAV progression as well as in decreased CAV-related events and mortality.

Background Evidence exists for racial/ethnic differences in left ventricular mass index (LVMI). How this translates to future cardiovascular disease (CVD) events is unknown. Hypothesis The impact of racial/ethnic differences in LVMI on incident cardiovascular outcomes could have potential implications for the optimization of risk stratification strategies. Methods Using the prospectively collected database of the Multi‐Ethnic Study of Atherosclerosis (MESA) involving 4 racial/ethnic groups (non‐Hispanic Whites, Chinese, Blacks, and Hispanics) free of CVD at baseline, we assessed for racial/ethnic differences in the relationship between LVMI and incident CVD using a Cox model. Results 5004 participants (mean age, 62 ± 10 years; 48% male) were included in this study. After an average follow‐up of 10.2 years, 369 (7.4%) CVD events occurred. Significant racial/ethnic differences existed in the relationship between LVMI and incident CVD ( P for interaction = 0.04). Notably, the relationship was strongest for Chinese (HR per 10‐unit increase in LVMI: 1.7, 95% CI: 1.1–2.8) and Hispanics (HR per 10‐unit increase in LVMI: 1.9, 95% CI: 1.5–2.2). Non‐Hispanic Whites demonstrated the lowest relationship (HR: 1.3, 95% CI: 1.1–1.5). LVMI values of 36.9 g/m 2.7 , 31.8 g/m 2.7 , 39.9 g/m 2.7 , and 41.7 g/m 2.7 were identified as optimal cutpoints for defining left ventricular hypertrophy (LVH) for non‐Hispanic Whites, Chinese, Blacks, and Hispanics, respectively. In secondary analysis of LVH (vs no LVH) using these optimal cutpoints, we found a similar pattern of association as above ( P for interaction = 0.04). For example, compared with those without LVH, Chinese with LVH had HR: 5.3, 95% CI: 1.6–17, whereas non‐Hispanic Whites with LVH had HR: 1.6, 95% CI: 1.2–2.1 for CVD events. Conclusions Among 4 races/ethnicities studied, LVMI has more prognostic utility predicting future CVD events for Chinese and Hispanics and is least significant for non‐Hispanic Whites.

Background To investigate heart failure ( HF ) hospitalization trends in the United States and change in trends after publication of management guidelines. Methods and Results Using data from the National Inpatient Sample and the US Census Bureau, annual national estimates in HF admissions and in‐hospital mortality were estimated for years 2001 to 2014, during which an estimated 57.4 million HF ‐associated admissions occurred. Rates (95% confidence intervals) of admissions and in‐hospital mortality among primary HF hospitalizations declined by an average annual rate of 3% (2.5%–3.5%) and 3.5% (2.9%–4.0%), respectively. Compared with 2001 to 2005, the average annual rate of decline in primary HF admissions was more in 2006 to 2009 (ie, 3.4% versus 1.1%; P =0.02). In 2010 to 2014, primary HF admission continued to decline by an average annual rate of 4.3% (95% confidence interval, 3.9%–5.1%), but this was not significantly different from 2006 to 2009 ( P =0.14). In contrast, there was no further decline in in‐hospital mortality trend after the guideline‐release years. For hospitalizations with HF as the secondary diagnosis, there was an upward trend in admissions in 2001 to 2005. However, the trend began to decline in 2006 to 2009, with an average annual rate of 2.4% (95% confidence interval, 0.8%–4%). Meanwhile, there was a consistent decline in in‐hospital mortality by an average annual rate of 3.7% (95% confidence interval, 3.3%–4.2%) during the study period, but the decline was more in 2006 to 2009 compared with 2001 to 2005 (ie, 5.4% versus 3.4%; P <0.001). Beyond 2009, admission and in‐hospital mortality rates continued to decline, although this was not significantly better than the preceding interval. Conclusions From 2001 to 2014, HF admission and in‐hospital mortality rates declined significantly in the United States; the greatest improvements coincided with the publication of the 2005 American College of Cardiology/American Heart Association HF guidelines.

Background Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post–left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. Methods and Results We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18–2.53; P =0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35–3.18; P =0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P <0.0001) and a significant reduction in requirements of DM medications. Conclusions DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

AbstractObjectivesTo assess the in‐hospital mortality and complications in female between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR).BackgroundFemale is one of the risk factors for increased adverse events in cardiac surgery.Methods and resultsNationwide Inpatient Sample database was queried from 2011 to 2014 for patients who underwent TAVR or SAVR in female patients. The primary endpoint was in‐hospital all‐cause mortality and second endpoints were perioperative complications. We performed a propensity score analysis to calculate the adjusted odds ratio (OR) for each outcome. Patients who had concomitant cardiac surgery and those who had TAVR or SAVR mainly for aortic regurgitation were excluded. Our query from 2011 to 2014 resulted in a total of 3,067 TAVR and 18,594 SAVR in female patients. TAVR patients were in general elder and had a higher burden of comorbidities. The primary endpoint was similar between TAVR and SAVR (4.2% vs. 3.9%, OR 1.0, P = 0.89). Compared to SAVR, female TAVR patients had less hemorrhage requiring transfusion (12% vs. 21%, OR 0.41, P < 0.001), perioperative cardiac arrest and nonfatal myocardial infarction (9.8% vs. 17%, OR 0.38, P < 0.001), respiratory complication (1.6% vs. 4.4%, OR 0.28, P < 0.001), post‐op sepsis (1.7% vs. 2.9%, OR 0.65, P = 0.03), acute myocardial infarction (3.0% vs. 4.9%, OR 0.60, P < 0.001), and acute kidney injury (15% vs. 18%, OR 0.62, P < 0.001). Conversely, female TAVR patients had significantly increased risk of new pacemaker implantation (11% vs. 5.9%, OR 1.7, P < 0.001) and use of extracorporeal membrane oxygenation (0.66% vs. 0.24%, OR 2.8, P < 0.001). TAVR patients had less nonroutine discharge. The median hospital cost was significantly higher in TAVR than SAVR (median $51,274 vs. $43,677, P < 0.001) but the length of stay was shorter (mean 7.8 days vs. 10.5 days).ConclusionsTAVR may be a better option for those patients with underlying comorbidities that predispose them at higher risk for complications that was less observed in TAVR group. However, higher cost and increased risk of need for extracorporeal membrane oxygenation, although rare, should be taken into consideration upon deciding the optimal mode for aortic valve replacement.

AbstractBackgroundTo assess the impact of post transcatheter aortic valve implantation (TAVI) mild paravalvular regurgitation (PVR) on mortality. More than moderate PVR after TAVI has decreased with the advent of new‐generation prosthetic valves. However, mild PVR remains common and its clinical impact has been inconsistent. We aimed to assess the impact of mild PVR through meta‐analysis.Methods and ResultsA systematic literature search was conducted through PUBMED and EMBSE. Manuscripts that reported hazard ratio (HR) with 95% confidence interval (CI) for clinical outcome of interest (all‐cause and cardiac mortality) has been included. Random‐effects model was used for calculation of HR. A total of 25 articles including total of 21,018 patients were finally included for quantitative synthesis (meta‐analysis). Our pooled analysis demonstrated higher all‐cause mortality in patients with mild PVR compared to none/trivial PVR (HR 1.26, 95%CI 1.11–1.43, I2=45%, p < 0.001) (follow up duration range 6 months to 5 years). Significant heterogeneity among studies was observed (p for heterogeneity = 0.005). Egger's test showed no evidence of publication bias. Cardiovascular mortality was increased in patients with mild PVR compared with none/trivial PVR (HR 1.28, 95%CI 1.05–1.57, I2=8%, p = 0.02) (follow up duration range 1–3 years).ConclusionsMild PVR was associated with increased all‐cause and cardiovascular mortality after TAVI. Whether further interventions in mild PVR is of benefit, has yet to be determined.

BackgroundThere is lack of evidence of the impact of varying season on heart failure (HF) hospitalization outcomes in the U.S.HypothesisHF hospitalization outcomes exhibit significant seasonal variation in the U.S.MethodsUsing data from the National Inpatient Sample (2011‐2013), seasonal variation was classified based on meteorological classification of Northern Hemisphere–Spring, Summer, Fall, & Winter–and analysis was conducted via multivariable‐adjusted mixed‐effect model.ResultsAn estimated 2.8 million adults were hospitalized for HF in the U.S. from 2011 to 2013. Of all hospitalizations, admissions were highest in Winter (27%), followed by Spring (26%), Fall (24%), and Summer (23%). The overall mortality rate was 3.1%. Compared with Spring, there was significantly lower mortality in Summer (odds ratio [OR]: 0.95, 95% CI: 0.91‐0.99) and Fall (OR: 0.94, 95% CI: 0.89‐0.98), but the highest mortality was in Winter (OR: 1.06, 95% CI: 1.02‐1.11). In addition, mean length of stay and median cost of hospitalization were highest in Winter (5.3 days, USD7459, respectively) and lowest in Summer (5.1 days, USD7181, respectively). However, age and sex differences existed (e.g. seasonal variation in inpatient mortality was only significant for patients age ≥65 years, and, comparedwith the Spring season, males had higher risk of inpatient mortality in Winter (OR: 1.10, 95% CI: 1.04‐1.17) and females had lower risk of inpatient mortality in Summer (OR: 0.94, 95% CI: 0.88‐1.00) and Fall (OR: 0.92, 95% CI: 0.87‐0.98).ConclusionsAmong HF patients in the U.S., hospitalization outcomes were worse in Winter but better in Summer.

AbstractObjectivesTo summarize the published data of combined transcatheter aortic and mitral valve intervention (CTAMVI).BackgroundCTAMVI, a combination of either transcatheter aortic valve replacement (TAVR) or transcatheter aortic valve‐in‐valve (TAViV) and transcatheter mitral valve replacement (TMVR), transcatheter mitral valve‐in‐valve/valve‐in‐ring (TMViV/ViR), or percutaneous mitral valve repair (PMVR) is an attractive alternative in high‐surgical risk patients with combined aortic and mitral valve disease. However, its procedural details and clinical outcomes have not been well described.MethodsWe performed a systematic review of all the published articles from PUBMED and EMBASE.ResultsA total of 37 studies with 60 patients were included. The indication for CTAMVI was high or inoperable surgical risk and symptomatic severe aortic stenosis (92%) or severe aortic regurgitation (8%) combined with moderate to severe/severe mitral stenosis (30%) or moderate/severe mitral regurgitation (65%) or both (5%). In majority of the cases, aortic valve intervention was performed prior to the mitral valve. Mortality rate were 25% for TAVR + TMVR (range 42 days to 10 months), 17% for TAVR + TMViV/ViR (range 13 days to 6 months), 0% for TAViV + TMViV/ViR (range 6–365 days), and 15% for TAVR/ViV + PMVR (range 17 days to 419 days). Significant (more than moderate) paravalvular regurgitation post‐procedure was rare.ConclusionsCTAMVI appears to confer reasonable clinical outcome. Further large study is warranted to clarify the optimal strategy, procedural details and clinical outcomes in the future.