Contrast-induced nephropathy (CIN) is a type of acute kidney injury associated with intravascular administration of iodinated contrast, usually reversible. Contrast agents are an essential component of invasive and noninvasive coronary angiography. These agents have been modified over time to enhance patient safety and tolerability, but adverse reactions still occur. CIN has been variably defined, as a rise in serum creatinine of 0.5 mg/dl, or a 25% increase in serum creatinine above baseline within 24-72 hours after the procedure. The incidence of CIN varies based on the definition used and risk profile of the patients. CIN is rare among patients with normal renal function at baseline. In low-risk patients, CIN occurs in 1-5%, whereas in higher-risk populations, the incidence can be as high as 30%. CIN is also associated with a 5- to 20-fold increased risk of other early adverse events including in-hospital myocardial infarction, target vessel occlusion, and early mortality. The main prevention strategies are adequate intravenous hydration before, during and after the procedure as well as restriction of contrast load with maximum volume approximately no more than three times the serum creatinine clearance. Recent observational and small prospective randomized trials demonstrate the reduction of CIN incidence with HMG-CoA enzyme inhibitors. In this systematic review and meta-analysis we explore the effects of statin administration in prevention of CIN.
Predictors and Clinical Outcomes of Vasoplegia in Patients Bridged to Heart Transplantation With Continuous‐Flow Left Ventricular Assist Devices
Background The presence of a durable left ventricular assist device ( LVAD ) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation ( HT ). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD . Methods and Results We identified 94 patients who underwent HT after bridging with continuous‐flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT . Patients with and without vasoplegia had similar preoperative LVAD , echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P =0.010), longer LVAD support (odds ratio: 1.06 per month; P =0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P =0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P =0.044) were independent predictors of vasoplegia. After mean follow‐up of 4.0 years after HT , vasoplegia was associated with increased risk of all‐cause mortality (hazard ratio: 5.20; 95% CI, 1.71–19.28; P =0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.
Management of Patients with Heart Failure: Focus on New Pharmaceutical and Device Options
Hospitalization rates and survival of patients with Heart Failure (HF) have improved. However, 5-year mortality rates remain high and the prevalence of the disease is rising likely due to aging of the population and advances in diagnosis and treatment of other acute and chronic cardiovascular diseases. Over the past three decades the therapeutic armamentarium of heart failure has improved substantially with development of medications targeting neuro-hormonal activation and devices preventing sudden cardiac death and improving cardiac synchrony. Recently, inhibition of angiotensin receptors and neprilysin as well as sinoatrial pacemaker modulating f-current, have been found safe and effective strategies that improve HF hospitalization rates and/or mortality. Antidiabetic agents inhibiting sodium-glucose co-transporters 2, result in natriuresis and osmotic diuresis and may further improve HF related outcomes. Furthermore, emerging therapies such as cardiac myosin activators, soluble guanylate cyclase stimulators and non-steroidal mineralocorticoid receptor antagonists are undergoing investigation in phase II and III studies of HF patients. Finally, rapid evolution of in the management of advanced HF has occurred with the application of second and third generation continuous flow left ventricular assist devices in clinical practice. Ongoing clinical studies will validate the safety and efficacy of emerging therapeutic strategies in HF population underrepresented in previous clinical trials.
Timing of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor Initiation and Allograft Vasculopathy Progression and Outcomes in Heart Transplant Recipients
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.
Racial/ethnic differences in the prognostic utility of left ventricular mass index for incident cardiovascular disease
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.
Therapeutic Approach to Patients with Heart Failure with Reduced Ejection Fraction and End-stage Renal Disease
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.
Impact of Diabetes Mellitus on Outcomes in Patients Supported With Left Ventricular Assist Devices
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.
Statins and Inflammation in Cardiovascular Disease
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.
Hospital outcomes of transcatheter versus surgical aortic valve replacement in female in the United States
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.