Feasibility of Intravascular Lithotripsy for the Treatment of Calcified Supra-Aortic Vessels: A Case Report and Literature Review.

PURPOSE: To report a case of coronary-subclavian steal syndrome (CSSS) due to a history of a left internal mammary artery (LIMA) to left anterior descending (LAD) artery coronary bypass (CABG) and a heavily calcified ostial left subclavian artery (LSA) occlusion, that was treated with intravascular lithotripsy (IVL) technique and to summarize the current trends of IVL treatment for supra-aortic vessels. CASE REPORT: A 64-year-old woman with progressive intermittent angina pectoris and a history of LIMA to LAD bypass underwent coronary angiography which demonstrated complete ostial occlusion of the LSA. Via brachial access, the patient underwent Shockwave IVL balloon treatment of the LSA and stent-graft implantation. At 9 months follow-up, the patient showed symptoms resolution, and duplex ultrasound (DUS) demonstrated a patent LSA. CONCLUSIONS: The Shockwave IVL system was demonstrated to be a feasible treatment and justified for selective cases of highly calcified lesions in supra-aortic vessels. The present case report and the literature review, in a total of 47 patients resulted in a high technical procedural success rate, with a low rate of complications. Future studies with larger cohorts are warranted to confirm these findings and standardize this technology in this particular vascular field. CLINICAL IMPACT: The present study exemplifies a case of recanalization of the left subclavian artery in a patient with coronary-subclavian steal syndrome with a heavily calcified ostial lesion treated with intravascular lithotripsy (IVL). In this paper, for the first time, a review of the contemporary literature on the use of IVL in supra-aortic vessels is reported, elucidating the feasibility of this technique in this vascular territory. Despite the heterogeneous features of the reported cases and the lack of a standardized protocol for the use of IVL in the management of highly calcified lesions of supra-aortic vessels, it was demonstrated to be a feasible technique, with a high technical success rate, being an advantageous tool for heavily calcified supra-aortic lesions.

Outcomes of Patients Undergoing PCI of Ostial Coronary Lesions: A Single-Center Study.

INTRODUCTION: Ostial coronary lesions are a subset of proximal coronary lesions, which are relatively more difficult to treat and were associated with worse clinical outcomes in the early percutaneous coronary intervention (PCI) era. Data regarding the outcomes of ostial lesions' PCI in the contemporary era are lacking. METHODS: We conducted a single-center, all-comer, prospective registry study, enrolling patients undergoing PCI with the use of contemporary drug-eluting stents (DES) between July 2016 and February 2018. Included in the present analysis were only patients treated for proximal lesions. Clinical outcomes were compared between patients undergoing PCI of ostial versus proximal nonostial lesions. The primary endpoint was target vessel revascularization (TVR). Secondary endpoints included target lesion revascularization (TLR) and major cardiovascular adverse events (MACE) at 12 months. RESULTS: A total of 334 (84.7% male, 67.3 ± 10.7 years) patients were included, of which 91 patients were treated for ostial lesions and 243 were treated for proximal nonostial lesions. Baseline and procedural characteristics were similar between the two groups. At 12 months, TVR and TLR were numerically higher among patients undergoing PCI of ostial versus nonostial lesions without reaching statistical significance (5.5% vs. 3.3%; p = 0.35 and 4.4% vs. 2.5%; p = 0.47, respectively). The rate of MACE was similar between the two groups. CONCLUSION: In patients undergoing PCI with the use of contemporary DES, clinical outcomes were similar among patients treated for ostial compared to proximal nonostial lesions. Larger studies are required to further evaluate the performance of contemporary DES in this subset of lesions.

Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker in Transcatheter Aortic Valve Implantation (TAVI) Patients.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value. OBJECTIVES: To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients. METHODS: We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality. RESULTS: Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09-1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure. CONCLUSIONS: NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.

Quinidine-Responsive Polymorphic Ventricular Tachycardia in Patients With Coronary Heart Disease.

BACKGROUND: Polymorphic ventricular tachycardia (VT) without QT prolongation is well described in patients without structural heart disease (mainly idiopathic ventricular fibrillation and Brugada syndrome) and in patients with acute ST-elevation myocardial infarction. METHODS: Retrospective study of patients with polymorphic VT related to coronary artery disease, but without evidence of acute myocardial ischemia. RESULTS: The authors identified 43 patients in whom polymorphic VT developed within days of an otherwise uncomplicated myocardial infarction or coronary revascularization procedure. The polymorphic VT events were invariably triggered by extrasystoles with short (364±36 ms) coupling interval. Arrhythmic storms (4-16 events of polymorphic VT deteriorating to ventricular fibrillation) occurred in 23 (53%) patients. These arrhythmic storms were always refractory to conventional antiarrhythmic therapy, including intravenous amiodarone, but invariably responded to quinidine therapy. In-hospital mortality was 17% for patients with arrhythmic storm. Patients treated with quinidine invariably survived to hospital discharge. During long-term follow-up (of 5.6±6 years; range, 1 month to 18 years), 3 (16%) of patients discharged without quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during quinidine therapy Conclusions: Arrhythmic storm with recurrent polymorphic VT in patients with coronary disease responds to quinidine therapy when other antiarrhythmic drugs (including intravenous amiodarone) fail.

Impact of preprocedural left ventricle hypertrophy and geometrical patterns on mortality following TAVR.

BACKGROUND: In contrast to surgical aortic valve replacement, left ventricle (LV) hypertrophy (LVH) had not been clearly associated with mortality following transcatheter aortic valve replacement (TAVR). METHODS: We performed a retrospective analysis of patients enrolled in the Israeli multicenter TAVR registry for whom preprocedural LV mass index (LVMI) data were available. Patients were divided into categories according to LVMI: normal LVMI and mild, moderate, and severe LVH. Mild LVH was regarded as the reference group. Additionally, LV geometry patterns were examined (concentric and eccentric LVH, and concentric remodeling). RESULTS: The cohort consisted of 1,559 patients, 46.5% male, with a mean age of 82.2 (±6.8) years and mean LVMI of 121 (±29) g/m2. Rates of normal LVMI and mild, moderate, and severe LVH were 31% (n = 485), 21% (n = 322), 18% (n = 279), and 30% (n = 475), respectively. Three-year mortality rates for normal LVMI and mild, moderate, and severe LVH were 19.8%, 18.3%, 23.7%, and 24.4%, respectively. Compared to mild LVH, moderate LVH and severe LVH were independently associated with an increased risk for all-cause mortality (hazard ratio [HR] 1.58, 95% CI 1.15-2.18, P = .005; HR 1.46, 95% CI 1.1-1.95, P = .009; respectively). Concentric LVH was independently associated with a decreased risk for mortality compared to normal LV geometry (HR 0.75, 95% CI 0.63-0.89, P = .001). Compared to concentric LVH, eccentric LVH was independently associated with a 33% increased risk for mortality (HR 1.33, 95% CI 1.11-1.60, P = .002). CONCLUSIONS: Mild concentric LVH confers a protective effect among patients with severe aortic stenosis undergoing TAVR. However, hypertrophy becomes maladaptive, and an increased baseline LVMI, eccentric pattern particularly, may be associated with all-cause mortality in this population.

Acute kidney injury after transcatheter aortic valve implantation and mortality risk-long-term follow-up.

BACKGROUND: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up. METHODS: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis. RESULTS: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022). CONCLUSIONS: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.

Forced diuresis with matched hydration during transcatheter aortic valve implantation for Reducing Acute Kidney Injury: a randomized, sham-controlled study (REDUCE-AKI).

AIMS: Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) and is associated with increased risk for short- and long-term mortality. In patients undergoing percutaneous coronary intervention (PCI), forced diuresis with matched hydration has been shown to reduce the incidence of AKI by ∼50%. The aim of the present study was to evaluate whether forced diuresis with matched intravenous hydration reduces AKI in patients undergoing TAVI. METHODS AND RESULTS: Reducing Acute Kidney Injury (REDUCE-AKI) was a single-centre, prospective, randomized, double-blind sham-controlled clinical trial, designed to examine the effect of an automated matched saline infusion with urine output for the prevention of AKI in patients undergoing TAVI. A total of 136 TAVI patients were randomized, 68 in each group. Mean age was 83.9 ± 5 years and 41.2% were males. There were no differences in baseline characteristics between the two groups. The rate of AKI was not statistically different between the groups (25% in the active group vs. 19.1% in the sham group, P = 0.408). There was a significant increase in long-term mortality in the active group (27.9% vs. 13. 2% HR 3.744, 95% CI 1.51-9.28; P = 0.004). The study was terminated prematurely by the Data Safety Monitoring Board for futility and a possible signal of harm. CONCLUSIONS: Unlike in PCI, forced diuresis with matched hydration does not prevent AKI in patients undergoing TAVI, and might be associated with increased long-term mortality. Future studies should focus on understanding the mechanisms behind these findings. CLINICALTRIALS.GOV REGISTRATION: NCT01866800, 30 April 2013.

Safety outcomes of new versus old generation transcatheter aortic valves.

OBJECTIVE: To compare procedural outcomes of transcatheter aortic valve implantation (TAVI) patients who were implanted with older versus newer generation valves. BACKGROUND: The current evidence base for improved safety of the newer commercially available TAVI valves is limited. METHODS: A retrospective analysis of the Israeli multicenter TAVI registry was performed. Patients were stratified by valve generation of four commercially available devices: Edwards Sapien (ESX) Edwards Sapien S3 (ES3), Medtronic CoreValve (MCV), and Medtronic Evolut R (MER). RESULTS: The cohort consisted of 737 patients with new generation valves (NGVs; ES3 n = 223; MER n = 514) and 1,869 with old generation valves (OGVs; MCV n = 1,181; ESX n = 688). Device success rates were significantly higher in NGV (97.5 versus 95.4%), with less post-procedural paravalvular leak (3 versus 5.8%), and valve mal-positioning (1.2 versus 3.4%); all P-values<0.05. There were no differences in rates of permanent pacemaker implantation, stroke or acute kidney injury (AKI) of any stage between the groups, although stage ≥2 AKI was more prevalent in NGV. After adjustment to significant differences in baseline patient and procedural characteristics, device success was higher (OR 1.86, 95% confidence interval (CI) 1.09-3.18, P = 0.023) and the 1-month safety outcome was significantly lower (OR 0.72, 95% CI 0.55-0.96, P = 0.025) for NGV. Device success was driven mainly by improved rates of PVL of ES3, while the safety outcome was mainly driven by improved rates of life-threatening bleeding and valve mal-positioning of MER. CONCLUSION: As compared to OGV, use of NGV for TAVI was associated with higher rates of device success and lower rates of adverse events.

Prognostic significance of aortic valve gradient in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

OBJECTIVE: To evaluate the effect of baseline aortic valve gradient (AVG) both as a continuous and a categorical variable on mortality in patients undergoing transcatheter aortic valve replacement (TAVR), focusing on the high-gradient severe aortic stenosis (AS) patients. BACKGROUND: Identifying new predictors of mortality in the TAVR population can help refine risk stratification and improve the patient selection process for this procedure. So far, AVG has mainly been studied as a categorical variable and there is a paucity of data on its prognostic value as a continuous variable, especially in patients with high AVG AS, who constitute the majority of patients referred for TAVR. METHODS: We analyzed data on 1,224 consecutive symptomatic severe AS patients, who underwent TAVR at 3 centers. The relation between pre-TAVR AVG and mortality was evaluated among all patients and in patients with high AVGs (mean AVG ≥40 mm Hg) using the Cox proportional hazard model adjusting for multiple variables. RESULTS: During a mean follow-up of 1.8 years, baseline AVG was inversely associated with mortality in the entire cohort and in patients with high AVG AS. By multivariable analysis, patients with mean AVG 40-60 mm Hg and >60 mm Hg had a respective 38% (P = 0.010) and 61% (P < 0.001) reduction in mortality compared to patients with mean AVG <40 mm Hg. Every 10 mm Hg increase in mean AVG was associated with 20% reduction in mortality (P < 0.001). Analyses among patients with high (mean AVG >40 mm Hg) and very high AVG AS (mean AVG >60 mm Hg) yielded similar results (HR = 0.88, P = 0.031, and HR = 0.80, P = 0.019, per 10 mm Hg increase in AVG, respectively). Using peak AVGs and an analysis restricted to patients without reduced ejection fraction yielded consistent results. CONCLUSIONS: Baseline AVGs show an inverse association with mortality post-TAVR. These results were consistent also in patients with high-gradient AS, suggesting that AVG can be used to identify patients most likely to benefit from TAVR.

Aortic regurgitation following transcatheter aortic valve replacement: Impact of preprocedural left ventricular diastolic filling patterns on late clinical outcomes.

OBJECTIVES: To investigate the impact of preprocedural left ventricular (LV) diastolic function on outcomes of patients with postprocedural aortic regurgitation (ARpost ) following transcatheter aortic valve replacement (TAVR). BACKGROUND: The predictors and mechanisms of the increased mortality in patients with ARpost are inadequately defined. METHODS: Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed. Preprocedural correlates of late outcomes (all-cause mortality and the composite of mortality, stroke, heart failure, and new-onset atrial fibrillation) were examined according to the presence and severity of ARpost . RESULTS: Of the 418 patients undergoing TAVR, ARpost was present in 212 (51%): mild 36%, moderate-severe 15%. Mean follow-up was 909 ± 489 days. All-cause mortality and composite endpoint rates were significantly increased in patients with moderate-severe ARpost compared with patients with either none or only mild ARpost (38, 22, 21%, P = 0.02; and, 56, 35, 40%, P = 0.01; respectively). Moderate-severe (though not mild) ARpost was independently associated with mortality and the composite endpoint (HR = 1.93 [95%CI 1.15-3.14], P = 0.01; HR = 1.85 [95%CI 1.22-2.77], P = 0.004], respectively). By multivariate analysis, preprocedural LV deceleration time (DT) < 160 ms was independently associated with the risk of all-cause mortality and the composite endpoint among patients with mild AR (HR = 1.74 [95%CI 1.14-2.60], P = 0.01; and, HR = 1.73 [95%CI 1.23-2.41], P = 0.002, respectively) and moderate-severe ARpost (HR = 1.81 [95%CI 1.28-2.51], P < 0.001; HR = 1.86 [95%CI 0.22-2.80], P = 0.004, respectively). CONCLUSIONS: Preprocedural impairment of LV filling, reflected by short DT, portends an adverse prognosis in TAVR patients who develop ARpost independently of other clinical and echocardiocardigraphic measures including AS severity and systolic LV function. © 2015 Wiley Periodicals, Inc.

HbA1c Levels and Long-Term Mortality in Patients Undergoing Coronary Angiography.

OBJECTIVES: Previous studies investigating the prognostic value of HbA1c in patients undergoing coronary angiography reported a mixed pattern of results. Therefore, we aimed to better define the prognostic power of HbA1c among coronary catheterized patients. METHODS: Patients undergoing coronary angiography (n = 3,749) were divided into four groups according to HbA1c levels (<5, 5-6, 6-7 and >7%). Cox regression models assessed long-term mortality after adjusting for multiple covariates. RESULTS: Baseline clinical profiles differed in HbA1c groups, with a higher prevalence of comorbidities in the groups with higher HbA1c levels. Median follow-up was 1,745 days (interquartile range 1,007-2,171). A J-shaped association curve was observed between HbA1c levels and all-cause mortality rates, with patients in the lowest and highest HbA1c groups suffering from significantly higher mortality rates compared to in-between groups (hazard ratio 1.9, 95% CI 1.32-2.74, p = 0.001, and hazard ratio 1.58, 95% CI 1.29-1.95, p < 0.001, for the lowest and highest HbA1c groups, respectively). This association persisted after adjustment for anemia, nutritional status, renal function, cardiovascular risk factors and inflammatory biomarkers. CONCLUSIONS: HbA1c levels <5 or >7% are predictors of all-cause mortality in patients undergoing coronary angiography.

High red blood cell distribution width and preclinical carotid atherosclerosis.

BACKGROUND: Preclinical carotid atherosclerosis is associated with future risk of stroke. Data regarding the correlation between carotid atherosclerosis and biomarkers, which might predict the risk for the disease has been inconsistent and conflicting. Red blood cell distribution width (RDW) is also related to adverse clinical outcomes. Studies examining the relationship between RDW and preclinical and clinical carotid atherosclerosis were non-conclusive. OBJECTIVE: To study the association between RDW and preclinical carotid atherosclerosis in a large heterogeneous cohort. METHODS: Patients underwent Doppler ultrasound of the common carotid artery and Carotid Intima Media Thickness (CIMT). Advanced CIMT software analyzed over 100 samples in each exam. Blood samples for RDW were obtained on the same day. Logistic regression was used to evaluate the correlation between RDW and preclinical carotid atherosclerosis. RESULTS: Five hundred and twenty-two consecutive patients were included, with a mean age of 6.6 ± 11. A cut-off value of 14.1% was used to differentiate between high and low RDW groups. The higher RDW group (RDW above 14.1%) was significantly older and with more cardiovascular risk factors. In a multivariate analysis, in all the patients including those treated by lipid modifying therapies, high RDW was significantly associated with advanced CIMT (OR = 2.35, CI 95% 1.28-4.30, p = 0.006). This association remained significant in subgroups of non-diabetic patients as well as patients not treated by lipid modifying drugs. RDW was also associated with significant carotid artery stenosis (OR = 1.77, CI 95% 1.12-2.82, p = 0.015). CONCLUSIONS: High RDW correlates with increased risk for preclinical and clinical carotid atherosclerosis.

Anemia in ST-Elevation Myocardial Infarction Patients with Markers of Inadequate Bone Marrow Response.

BACKGROUND: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure. OBJECTIVES: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts. METHODS: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated. RESULTS: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x 103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x 103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients, with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). CONCLUSIONS: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response.

Impact of carotid atherosclerosis on the risk of adverse cardiac events in patients with and without coronary disease.

BACKGROUND AND PURPOSE: Carotid atherosclerosis (CA) is reportedly a strong predictor of imminent cardiac events even in the absence of established coronary artery disease (CAD). We examined the differential impact of CA on the risk of major adverse cardiovascular events in patients with and without CAD diagnosed angiographically. METHODS: We conducted a follow-up survey of 1391 patients who underwent clinically driven coronary angiography and a same-day carotid ultrasound and Doppler study. Definitions of CAD, CA, and carotid artery stenosis were in accordance with current practice guidelines. RESULTS: Of 1391 patients, angiographic CAD was present in 1105 (79%) patients. Mean and median follow-up was 1574 and 1702 days, respectively. Rates of the primary composite major adverse cardiovascular event end point were higher among patients with CAD compared with those without CAD (48% versus 20%; P<0.001), whereas the rates of all-cause mortality (10% versus 9%; P=0.81) and stroke (7% versus 5%; P=0.3) did not differ significantly between both groups. Carotid artery stenosis and CA were associated with an increased risk of the composite major adverse cardiovascular event end point among patients without CAD (hazard ratio=3.17 [95% confidence interval, 1.52-6.60]; P<0.01; and hazard ratio=1.69 [0.95-3.01]; P=0.07, respectively) though not in patients with CAD. Carotid artery stenosis was associated with an increased risk of all-cause mortality among patients without CAD (hazard ratio=2.93 [1.09-7.87]; P=0.03]) though not among those with CAD. CONCLUSIONS: CA and carotid artery stenosis are independent predictors of major adverse cardiovascular event in patients undergoing coronary angiography. The prognostic implications of carotid disease are imparted predominantly in patients without pre-existent CAD.

Decline in serum cholinesterase activities predicts 2-year major adverse cardiac events.

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09-3.15, p = 0.02] and 2.21 [95% CI 1.22-4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

Prevalence and predictors of carotid artery stenosis in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: Our aim was to analyze the prevalence and predictors of Carotid artery stenosis (CAS) in patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND: CAS is associated with the risk of periprocedural stroke in patients undergoing cardiac surgery. However, little is known about the prevalence of and clinical significance of CAS in the setting of TAVI. METHODS: Consecutive patients undergoing a carotid Doppler study the day before TAVI were followed prospectively. CAS was defined in accordance with current practice guidelines. Logistic regression models were used to identify independent correlates of CAS. RESULTS: The study included 171 patients (age 82 ± 6, male gender 47%). Carotid atherosclerosis (CA, defined as any carotid plaque) was present in 164 (96%) of patients, and CAS (peak systolic velocity [PSV] ≥ 125 cm/sec; ≥50% diameter stenosis) in 57 (33%) patients. Severe CAS (PSV ≥ 230 cm/sec; ≥70% stenosis, or near occlusion) was found in 15 (9%) patients. By multivariate analysis, smoking and a higher Euroscore independently predicted the presence of CAS. Patients in the present TAVI cohort had a significantly higher prevalence of both unilateral and bilateral CAS ≥ 50% than those in a previously reported cohort (n = 494 patients, age ≥ 70) undergoing clinically driven coronary angiography (33% vs. 20%, OR = 1.9, P = 0.001; and, 13% vs. 6%, OR = 2.3, P = 0.003, respectively). CAS was not independently associated with 30-day mortality or stroke rates. CONCLUSIONS: The prevalence of CAS in patients undergoing TAVI is high, exceeding that observed in patients undergoing catheterization for coronary indications. The impact of CAS on clinical outcomes following TAVI merits further research.

Comparison of early and late outcomes of TAVI alone compared to TAVI plus PCI in aortic stenosis patients with and without coronary artery disease.

OBJECTIVES: To assess the safety and effectiveness of performing percutaneous coronary intervention (PCI) before transcatheter aortic valve implantation (TAVI). BACKGROUND: The presence of coronary artery disease (CAD) negatively impact procedural outcomes and long-term survival after (TAVI). The management of obstructive CAD before TAVI is not yet well established. METHODS: Patients with severe symptomatic aortic stenosis (AS) (n = 249) that underwent TAVI were divided into two groups: patients with CAD (subdivided to patients treated with TAVI alone and to patients that underwent PCI before TAVI) and patients with isolated AS. Procedural endpoints, device success and adverse events were considered according to the Valve Academic Research Consortium (VARC) definitions. RESULTS: Of a cohort of 249 consecutive patients with mean age of 83.2 ± 5.5 years, 83 patients with AS + CAD were treated with TAVI alone, 61 patients with AS + CAD underwent PCI before TAVI and 105 patients underwent TAVI for isolated AS. The mean duration of follow-up was 17 months (range: 6-36 months). Despite a significantly higher logistic EuroScore of the AS+CAD group compared to the AS alone group (30.1 vs. 21.1 P < 0. 001), the overall VARC-adjudicated endpoints did not differ between the groups. All-cause mortality at 30-days was 1.6% for patients with AS+CAD treated with PCI compared to 2.9% for patients with AS alone (P = 1). CONCLUSIONS: Performing PCI before TAVI in high-risk elderly patients with significant CAD and severe AS is feasible and safe. This combined treatment approach did not increase the periprocedural risk for complications or the all-cause mortality.

Red blood cell distribution width and 3-year outcome in patients undergoing cardiac catheterization.

Red blood cell distribution width (RDW), which is routinely reported in complete blood counts, is a measure of the variability in size of circulating erythrocytes. RDW is a novel, independent predictor of prognosis in patients with cardiovascular diseases. The aim of the present study was to evaluate the significance of this biomarker in a relatively large cohort of patients, and to assess its association with a more severe underlying cardiovascular disease. A cohort of 3,222 consecutive patients undergoing coronary angiography was divided according RDW median. The association between RDW and 3-year outcome in the context of other predictors was assessed using Cox's proportional hazards analysis. Patients with elevated RDWs were older, had higher body mass indices, and had more cardiovascular risk factors and more cardiovascular diseases. The total rate of mortality, MI and stroke (MACE) was 7.7% (120 events) in the lower RDW group, and 18.2% (303 events) in the higher RDW group, p < 0.001. Following adjustment for multiple background risk factors, medications, and laboratory results, the RDW value was independently associated with worse outcome (HR = 1.12, 95% CI 1.07-1.18, p < 0.001, for each 1% increase in RDW). Elevated RDW values are independently associated with adverse 3-year outcome in patients undergoing coronary angiography.

Lipoprotein(a) Levels in Severe Aortic Stenosis Referred for Transcatheter Aortic Valve Implantation Compared to Controls.

Background: Limited observational reports link elevated lipoprotein(a) (Lp[a]) levels to aortic stenosis (AS) or to disease progression. Data on large cohorts of verified severe AS patients are lacking. Objectives: The purpose of the study was to characterize Lp(a) levels of severe AS patients referred to transcatheter aortic valve implantation (TAVI) and compare them to a large cohort of Lp(a) samples derived from the general population. Methods: Lp(a) levels obtained from frozen serum samples of TAVI patients between 2012 and 2017 were compared to a control group for whom Lp(a) levels were obtained for any reason and stratified by gender. Multivariable binary logistic regression analyses were conducted to investigate associations between younger age at TAVI and an Lp(a) cutoff of 50 mg/dL. Results: Lp(a) levels of 503 TAVI were compared to 25,343 controls. Patients in the AS group had mildly higher median Lp(a) levels compared to controls (20.5 vs 18.7 mg/dL, P = 0.04). Lp(a) levels in males with severe AS were higher than controls (19.9 vs 16.6 mg/dL, P = 0.04). Females had a nonsignificant difference (22.1 vs 21.3 mg/dL, P = 0.87). In multivariable analysis, an Lp(a) cutoff of above 50 mg/dL was not associated with an earlier age at TAVI (beta: 1.04; 95% CI: 0.42-2.57; P = 0.94). Conclusions: Median Lp(a) levels were only mildly higher in severe AS patients undergoing TAVI in comparison to a large control group, mainly driven by higher Lp(a) levels in males. Higher Lp(a) levels were not associated with an earlier age at TAVI, rejecting its association with an accelerated disease progression.

Evaluation of coronary disease among patients undergoing transcatheter aortic valve implantation: propensity score matching analysis.

BACKGROUND: Chronic coronary syndrome (CCS) is common among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Current guidelines recommend performance of percutaneous coronary intervention (PCI) of any > 70% proximal coronary lesions prior to TAVI. AIMS: To evaluate the outcomes of two diagnostic approaches for CCS clearance pre-TAVI and to determine the reduction in the need of invasive angiography (IA). METHODS: We investigated 2219 patients undergoing TAVI for severe aortic stenosis at two large centers with different pre-procedural strategies for CCS assessment: pre-TAVI computed tomography angiography (CTA) with selective invasive angiography according to CTA results or mandatory IA. We preformed propensity score matching analysis using a 1:1 ratio. The final study cohort included 870 matched patients. Peri-procedural complications were documented according to the VARC-2 criteria. Mortality rates were prospectively documented. RESULTS: Mean age of the study population was 82 ± 7, of whom 55% were female. Patients in the IA group had significantly higher rates of pre-TAVI PCI compared to the CTA group (39% vs. 22%, p < 0.001). Following TAVI, peri-procedural myocardial infarction (MI) rates were similar between the two groups (0.3% vs. 0.7%, p value = 0.41), but spontaneous MI were significantly lower among the IA group (0% vs. 1.3%, p value = 0.03). Kaplan-Meier's survival analysis found that the cumulative probability of 1-year morality was similar between the two groups (p value log rank = 0.65). Cox regression analysis did not find association between CCS clearance strategy and outcome. CONCLUSIONS: In elderly patients, CTA-driven approach for CCS evaluation pre-TAVI is a valid strategy with similar outcome as compared to invasive approach. CTA strategy significantly reduces invasive procedures rates without compromising patient's outcome.