Zach Rozenbaum

Impact of Right Ventricular Dysfunction and Tricuspid Regurgitation on Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) may coexist with aortic stenosis. The aim of this study was to assess the association between RV dysfunction, TR, associated comorbidities, and outcomes following transcatheter aortic valve replacement (TAVR). Methods: A retrospective analysis was conducted of baseline and 6‐month clinical and echocardiographic parameters, including TR grade, RV size (grade, end‐diastolic and end‐systolic areas, annular diameter), and function (grade, tricuspid annular plane systolic excursion [TAPSE], fractional area change, Tei index), in 519 consecutive TAVR patients. Results: The prevalence of moderate or greater TR was 11% (n = 59). Although TR was associated with increased mortality (P = .02) in unadjusted analysis, it did not demonstrate an independent association with outcome when adjusted for RV dysfunction (TAPSE; P = .30) or multiple clinical parameters (P ≥ .20). RV parameters associated with poor outcomes included TAPSE (P = .006) and Tei index (P = .005). TAPSE was associated with lower survival even when adjusted for TR (P = .009) and all clinical parameters (P = .01). Persistence of moderate or greater TR 6 months after TAVR seemed to be associated with lower survival (P = .02), even when adjusted for clinical and RV parameters (P = .07). Conclusions: TR in association with aortic stenosis is frequently progressive despite TAVR but is not independently associated with outcomes. RV function is a stronger driver of adverse outcomes compared with TR itself, and RV quantitative rather than qualitative evaluation is the key to stratify these patients.

CHA2DS2-VASc score and clinical outcomes of patients with acute coronary syndrome.

BACKGROUND The CHA2DS2-VASc score has been recommended for the assessment of thromboembolic risk in patients with atrial fibrillation. HYPOTHESIS The CHA2DS2-VASc score may be associated with adverse outcomes in patients with ACS. METHODS Included were patients with ACS enrolled in the Acute Coronary Syndrome Israeli biennial Surveys (ACSIS) during 2000-2013. Patients were divided into 4 groups according to their CHA2DS2-VASc score (0 or 1, 2 or 3, 4 or 5, and >5). The primary endpoint was 1-year all-cause mortality. RESULTS The 13,422 patients had a mean age of 63.5±13years and included 25.8% females. Higher CHA2DS2-VASc score was associated with a significant increase in 1-year mortality. Patients with a CHA2DS2-VASc score >5 had the highest 1-year mortality risk that was 6-fold higher compared to patients with a score of 0 to 1 (hazard ratio=6, 95% CI=4.1-8.8, p<0.0001). However, even an intermediate CHA2DS2-VASc score of 2-3 was associated with a significant 2.6-fold increase in 1-year mortality. Patients with a higher CHA2DS2-VASc score were less frequently selected for an invasive strategy with an early coronary angiogram and subsequent angioplasty and were less commonly treated with the guideline-based medications. However, differences in outcomes remained significant following a multivariate analysis suggesting that these variations in therapy can only partially explain the differences in outcomes. CONCLUSIONS Higher CHA2DS2-VASc score identifies high-risk patients that may be overlooked by existing scores. Further studies are needed in order to evaluate whether the CHA2DS2-VASc score may be used together with the GRACE score for an improved risk assessment of ACS patients.

Prevalence and Significance of Unrecognized Renal Dysfunction in Patients with Acute Coronary Syndrome

BACKGROUND Unrecognized renal insufficiency, defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) in the presence of normal serum creatinine, is common among patients with acute coronary syndrome. We aimed to determine the prevalence and clinical significance of unrecognized renal insufficiency in a large unselected population of patients with acute coronary syndrome. METHODS The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli biennial Surveys during 2000-2013. The estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease formula. Patients were stratified into 3 groups: 1) normal renal function (estimated glomerular filtration rates ≥60 mL/min/1/73 m(2)); 2) unrecognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≤1.2 mg/dL); and 3) recognized renal insufficiency (estimated glomerular filtration rates <60 mL/min/1/73 m(2) with serum creatinine ≥1.2 mg/dL). The primary endpoint was all-cause mortality at 1 year. RESULTS Included in the study were 12,830 acute coronary syndrome patients. Unrecognized renal insufficiency was present in 2536 (19.8%). Patients with unrecognized renal insufficiency were older and more frequently females. All-cause mortality rates at 1 year were highest among patients with recognized renal insufficiency, followed by patients with unrecognized renal insufficiency, with the lowest mortality rates observed in patients with normal renal function (19.4%, 9.9%, and 3.3%, respectively, P <.0001). Despite their increased risk, patients with renal insufficiency were less frequently referred for coronary angiography and were less commonly treated with guideline-based cardiovascular medications. CONCLUSIONS Acute coronary syndrome patients with unrecognized renal insufficiency should be considered as a high-risk population. The question of whether this group would benefit from a more aggressive therapeutic approach should still be evaluated.

Balloon dilatation and outcome among patients undergoing trans-femoral aortic valve replacement

BACKGROUND Balloon pre-dilatation before transcatheter aortic valve replacement (TAVR) is performed at the discretion of the treating physician. Clinical data assessing the implications of this step on procedural outcomes are limited. METHODS We conducted a retrospective analysis of 1164 consecutive TAVR patients in the Israeli multicenter TAVR registry (Sheba, Rabin, and Tel Aviv Medical Centers) between the years 2008 and 2014. Patients were divided to those who underwent balloon pre-dilation (n=1026) versus those who did not (n=138). RESULTS Rates of balloon pre-dilation decreased from 95% in 2008-2011 to 59% in 2014 (p for trend=0.002). Baseline characteristics between groups were similar except for more smoking (22% vs. 8%, p=0.008), less past CABG (18% vs. 26%, p=0.016), less diabetes mellitus (35% vs. 45%, p=0.01), and lower STS mortality scores (5.2±3.7 vs. 6.1±3.5, p=0.006) in the pre-dilatation group. The pre-dilation group included less patients with moderate to severely depressed LVEF (7% vs. 16%, p<0.001) and higher aortic peak gradients (76.9±22.7mmHg vs. 71.4±24.3mmHg, p=0.01). Stroke rates were comparable in both groups (2.5% vs. 3%, p=0.8), but pre-dilation was associated with lower rates of balloon post-dilatation (9% vs. 26%, p<0.001). On multivariate analysis, balloon pre-dilatation was not a predictor of device success or any post-procedural complications (p=0.07). CONCLUSIONS Balloon pre-dilatation was not associated with procedural adverse events and may decrease the need for balloon post-dilatation. The results of the present study support the current practice to perform liberally balloon pre-dilatation prior to valve implantation.

Admission plasma glucose levels within the normal to mildly impaired range and the outcome of patients with acute coronary syndrome.

Background: Elevated admission plasma glucose levels >140 mg/dl are associated with adverse clinical outcomes in both diabetic and non-diabetic patients admitted with acute coronary syndrome (ACS). We aimed to evaluate the association between admission plasma glucose levels <140 mg/dl and the outcome of non-diabetic patients admitted with acute coronary syndrome. Methods: The study population consisted of patients with acute coronary syndrome included in the Acute Coronary Syndrome Israeli Survey during 2000–2013. Diabetic patients were excluded. The primary endpoint was all-cause mortality at one year. Results: The 4520 patients had a mean age of 61.7±13.5 years and were stratified into four quartiles according to admission plasma glucose (60–94, 95–105, 106–119, 120–140 mg/dl). Patients with higher admission plasma glucose were older and included a higher percentage of smokers. In addition, the higher the glucose so also did they have a poorer risk factor profile including a higher body mass index, total and low-density lipoprotein cholesterol and triglyceride levels, and lower high-density lipoprotein cholesterol levels. During the first year 5.2% of patients died. A comparison of one-year mortality according to admission plasma glucose quartiles demonstrated a significant and progressive increase in mortality risk as admission plasma glucose rose (3.5%, 4.1%, 6.1%, 6.4%, respectively, p=0.001). However, this association lost its clinical significance following a multivariate analysis (p=0.08). Conclusions: High admission plasma glucose levels within the normal to mildly impaired range are associated with increased one-year mortality in non-diabetic acute coronary syndrome patients. However, the higher glucose level is probably not the cause for the adverse outcome but rather a marker for high risk. Our findings support the definition of 140 mg/dl as the cutoff for clinically acceptable admission glucose levels in patients with acute coronary syndrome.

Discriminating Circulatory Problems From Deconditioning: Echocardiographic and Cardiopulmonary Exercise Test Analysis

Background: Discriminating circulatory problems with reduced stroke volume (SV) from deconditioning, in which the muscles cannot consume oxygen normally, by gas exchange parameters is difficult. Methods: We performed combined stress echocardiography (SE) and cardiopulmonary exercise tests (CPET) in 110 patients (20 with normal effort capacity, 54 with attenuated SV response, and 36 with deconditioning) to evaluate multiple hemodynamic parameters and oxygen content difference (A‐Symbolo2 Diff) in four predefined activity levels to assess which of the gas measures may help in the discrimination. Symbol. No caption available. Results: Reduced anaerobic threshold (AT), low unchanging peak oxygen pulse, periodic breathing, shallow &Dgr; peak oxygen consumption (Symbolo2)/&Dgr;work rate (WR) ratio, and high expired volume per unit time/carbon dioxide production (Symbole/Symbolco2) slope were all associated with abnormal SV response (P < .05 for all). The best discriminator was Symbole/Symbolco2 slope to Symbolo2 ratio (≥ 2.7; area under the curve [AUC], 0.79; P < .0001). The optimal gas exchange model included &Dgr;Symbolo2/&Dgr;WR < 8.6; Symbole/Symbolco2 slope to peak Symbolo2 ratio ≥ 2.7, and periodic breathing (AUC of 0.84; P < .0001). Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Conclusions: The best single gas exchange parameter to discriminate between circulatory problems and deconditioning is Symbole/Symbolco2 slope to peak SymbolO2 ratio. Combining it with &Dgr;Symbolo2/&Dgr;WR and periodic breathing improves the discriminative ability. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available.

Ultra-Low Contrast Volume for Patients with Advanced Chronic Kidney Disease Undergoing Coronary Procedures

Background/Aims: Contrast induced nephropathy (CIN) is associated with adverse clinical outcomes in patients undergoing coronary interventions, particularly in patients with advanced chronic kidney. The study was aimed to assess the real-life feasibility and safety of ultra-low volume coronary procedures in patients with advanced chronic kidney disease. Methods: A prospective study that included patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2) was conducted. Coronary procedures were performed using an ultra-low contrast volume technique. Results: The 30 patients had a mean eGFR of 31.8(±8) mL/min/1.73 m2. Indications for coronary angiography were non-ST elevation myocardial infarction (63.3%), unstable (20%), and stable angina pectoris (16.7%). Median contrast volume for diagnostic coronary angiography was 13 mL (interquartile ranges [IQR] 12–14.9), and an additional 13 mL (IQR 8.8–14.3) for percutaneous coronary intervention (PCI). In 3 patients (10%), a ≥25% increase was demonstrated in serum cystatin C levels 48 h following the procedure. None of the patients demonstrated a ≥25% increase in serum creatinine levels at 48 h. Following 6 months, no patient required renal replacement therapy or unplanned coronary intervention. Conclusions: In patients with advanced chronic kidney disease, the ultra-low contrast technique is feasible and effective and can be used safely without a significant deterioration in renal function. This technique may increase the utilization of PCI in high-risk coronary patients with chronic kidney disease.

Downregulated Expression of TRPV2 in Peripheral Blood Cells following Acute Myocardial Infarction Is Inversely Correlated with Serum Levels of CRP and Troponin I

Objectives: We have recently shown that the transient receptor potential vanilloid 2 (TRPV2) channel is exclusively upregulated in rat/murine peri-infarct monocytes/macrophages following an acute myocardial infarction (AMI), and that this overexpression might be detrimental for cardiac recovery. We aimed to characterize the expression levels of TRPV2 in peripheral blood mononuclear cells (PBMCs) of AMI patients relative to individuals with normal coronaries, and to analyze potential associations with inflammatory and cardiac ischemic markers. Methods: Patients who underwent coronary angiography due to AMI or chest pain were prospectively included. PBMCs were isolated from whole blood by Ficoll gradient centrifugation. TRPV2 expression was analyzed by real-time PCR. C-reactive protein (CRP) and troponin I (TpI) levels were determined at the central chemistry laboratory; interleukin 6 and insulin-like growth factor (IGF)-1 levels were tested by ELISA. Results: Following AMI, the number of TRPV2-expressing PBMCs was reduced when compared to in patients with normal coronaries. An inverse correlation was documented between the numbers of circulating macrophages and TRPV2 expression. Additionally, TRPV2 expression was inversely correlated with CRP and TpI and directly correlated with serum IGF-1. Conclusions: We assume that peripheral TRPV2 downregulation occurs concomitantly with the accumulation of TRPV2-white blood cells in the peri-infarct zone. TRPV2 may thus represent a novel target for treatment in the acute phase after MI.

Very Small Left Atrial Volume as a Marker for Mortality in Patients Undergoing Nongated Computed Tomography Pulmonary Angiography

Objectives: To evaluate the association between very small left atria (VSLA) on nongated computed tomography pulmonary angiography (CTPA) and mortality in patients without pulmonary embolism (PE). Methods: Patients who underwent nongated CTPA between 2011 and 2015 in order to rule out PE, and had an echocardiogram within 24 h of the CTPA, were retrospectively identified. The left atrial volume of nongated CTPA was calculated using automatic 4-chamber volumetric analysis software. The association between the lowest 5th percentile of the left atrial volume index, referred to as the VSLA group, and mortality was investigated after adjustment for age, gender, background diseases, and laboratory values. Results: The study cohort included 241 patients. Patients with VSLA had a left atrial volume index <24 mL/m2 (n = 11). Demographics and background diseases did not differ between the study groups. The median follow-up was 22.7 months (IQR 0.03-54.3). VSLA was an independent predictor of mortality (HRadj = 3.6; 95% CI 1.46-8.87; p = 0.005), along with malignancy (HRadj = 2.28; 95% CI 1.32-3.93; p = 0.003) and lower hemoglobin (HRadj = 0.86; 95% CI 0.76-0.99; p = 0.032). Conclusions: Our findings suggest that VSLA on nongated CTPA may serve as a marker for mortality. The use of CTPA volumetric analysis can help risk stratification in patients with dyspnea and no PE.

Pathological presentation of cardiac mitochondria in a rat model for chronic kidney disease

Background Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. Methods Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB). Cardiac function was assessed by echocardiography and cardiac sections were evaluated for interstitial fibrosis and cardiomyocytes’ hypertrophy. Electron microscopy was used to explore the spatial organization of the cardiomyocytes. Expression levels of mitochondrial content and activity markers were tested in order to delineate the underlying mechanisms for mitochondrial pathology in the CKD setting with or without ARB administration. Results CKD per-se resulted in induced cardiac interstitial fibrosis and cardiomyocytes’ hypertrophy combined with a marked disruption of the mitochondrial structure. Moreover, CKD led to enhanced cytochrome C leakage to the cytosol and to enhanced PARP-1 cleavage which are associated with cellular apoptosis. ARB treatment did not improve kidney function but markedly reduced left ventricular mass, cardiomyocytes’ hypertrophy and interstitial fibrosis. Interestingly, ARB administration improved the spatial organization of cardiac mitochondria and reduced their increased volume compared to untreated CKD animals. Nevertheless, ARB did not improve mitochondrial content, mitochondrial biogenesis or the respiratory enzyme activity. ARB mildly upregulated protein levels of mitochondrial fusion-related proteins. Conclusions CKD results in cardiac pathological changes combined with mitochondrial damage and elevated apoptotic markers. We anticipate that the increased mitochondrial volume mainly represents mitochondrial swelling that occurs during the pathological process of cardiac hypertrophy. Chronic administration of ARB may improve the pathological appearance of the heart. Further recognition of the molecular pathways leading to mitochondrial insult and appropriate intervention is of crucial importance.