Comparison of Catheterization Versus Echocardiographic-Based Gradients in Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation.

OBJECTIVES: In patients with transcatheter aortic valve implantation (TAVI), accurate assessment of gradients is important to assess valve function and durability, which drives clinical decision-making. We sought to evaluate discrepancies in aortic valve mean gradients with balloon-expandable and self-expanding TAVI. METHODS: We retrospectively reviewed 507 patients that underwent TAVI and compared mean gradients by catheterization to transthoracic Doppler echocardiography. RESULTS: Mean gradients by Doppler in balloon-expandable (11.0 ± 5.8 mm Hg) and self-expanding devices (8.7 ± 4.5 mm Hg) were significantly higher than catheterization (3.2 ± 4.0 mm Hg vs 3.5 ± 4.1 mm Hg, respectively; P<.001). In a subgroup analysis of skirted valves, Doppler gradients in balloon-expandable (9.8 ± 4.4 mm Hg) and self-expanding devices (8.6 ± 5.1 mm Hg) were significantly higher than catheterization (3.5 ± 4.1 mm Hg vs 4.2 ± 4.8 mm Hg, respectively; P<.001). When the effect of valve size on gradients was analyzed, Doppler gradients were significantly higher than catheterization for all comparisons. When indexed for valve size, patients with large aortas who received a balloon-expandable TAVI had greater pressure differential than those who received a self-expanding TAVI (8.24 ± 0.46 mm Hg vs 5.16 ± 0.66 mm Hg; P<.001). This trend was not seen in patients with a small aorta-to-valve index. CONCLUSION: Following TAVI, aortic valve mean gradients acquired by Doppler were higher than catheterization and the discrepancy was more pronounced in balloon-expandable than self-expanding prostheses. These differences persist in skirted valves and across valve sizes. These observations may reflect periprocedural hemodynamic changes, differences between prosthetic flow acceleration, and/or pressure recovery.

Slope of left ventricular filling as an index of valvular and paravalvular regurgitation in native and prosthetic aortic valves.

BACKGROUND: Precise quantification of paravalvular aortic regurgitation (PAR) is challenging. Aortic regurgitation index (AR index) has been validated in transcatheter aortic valve replacement (TAVR) cohorts; however, accuracy is limited by heart rate dependency. Diastolic pressure time (DPT) index has been suggested as an alternative and also predicts mortality after TAVR. We chose to evaluate the left ventricular diastolic filling slope (LVDFS) as a surrogate of AR, and suggest it is less heart rate dependent than the AR index and comparable to DPT index. METHODS: For initial validation, we compared the LVDFS between three cohorts of patients with native aortic valves referred for hemodynamic assessment: (1) Patients without AR; (2) moderate AR; and (3) severe AR. We then retrospectively identified TAVR patients between January 2012 and 2017, and compared LVDFS to echocardiographic PAR. RESULTS: In both TAVR patients and those patients with native aortic valve disease, the LVDFS showed a stepwise increase with increasing echocardiographic AR severity. When compared to AR or DPT indices, LVDFS better discriminated the degree of AR in native valves and post-TAVR when AR is primarily paravalvular. Additionally, the slope did not considerably change across a spectrum of heart rates in both native and post-TAVR populations. CONCLUSIONS: The LVDFS is a simple, reproducible metric that can be operationalized in patients undergoing TAVR, as well as those with native valve regurgitation. Additional studies are necessary to determine the relationship between LVDFS and post-TAVR outcomes.

Advanced chronic kidney disease: Relationship to outcomes post-TAVR, a meta-analysis.

Chronic kidney disease (CKD) is associated with worse outcomes in high-surgical-risk patients undergoing transcatheter aortic valve replacement (TAVR). However, it is unclear whether this relationship is apparent in lower-surgical-risk patients. We sought to analyze existing literature to assess whether or not advanced CKD is associated with increased mortality or a greater incidence of adverse events (specifically major stroke, bleeding, and vascular complications). We searched PubMed and Embase (2008-2017) for relevant studies. Studies with <1 year follow-up and those not evaluating advanced CKD or outcomes post-TAVR were excluded. Our co-primary endpoints were the incidence of short-term mortality (defined as in-hospital or 30-day mortality) and long-term mortality (1 year). Our secondary endpoints included incidence of major stroke, life-threatening bleeding, and major vascular complications. Eleven observational studies with a total population of 10709 patients met the selection criteria. Among patients with CKD there was an increased risk of short- and long-term mortality in high-surgical-risk patients who underwent TAVR (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.22-1.88 and HR: 1.56, 95% CI: 1.38-1.77, respectively; P < 0.01). However, there was no association between CKD and mortality in low- to intermediate-risk patients (HR: 1.35, 95% CI: 0.98-1.84, P = 0.06 in short-term and HR: 1.08, 95% CI: 0.92-1.27, P = 0.34 in long-term). In low- to intermediate-risk TAVR patients, advanced CKD is not associated with increased mortality or poorer safety outcomes. These findings should be factored into the clinical decision-making process regarding TAVR candidacy.

Recurrent Spontaneous Coronary Artery Dissection in 4 Vascular Territories.

Spontaneous coronary artery dissection, a rare cause of acute coronary syndrome, is due to nonatherosclerotic coronary events and is probably underrecognized as a cause of myocardial infarction. The condition typically affects premenopausal women who are otherwise healthy. Among more than 1,200 reported cases, recurrent dissection has been described 63 times, and only 3 reports have documented multiple episodes of dissection involving different vascular territories. We present the case of a woman in her 30s who, over a 9-year period, presented 4 times with coronary dissection in different vascular territories. She was first treated conservatively, then with stents, and ultimately by means of coronary artery bypass grafting. In addition to this case, we discuss this rare condition and its management.

A meta-analysis of reduced leaflet motion for surgical and transcatheter aortic valves: Relationship to cerebrovascular events and valve degeneration.

BACKGROUND: Reduced leaflet motion (RLM) of transcatheter aortic valves (TAV) is observed in up to 4% of cases with similar frequency in surgical valves, with an overall incidence that differs based on prosthesis type and size. This phenomenon likely represents subclinical leaflet thrombosis. Herein we sought to analyze the existing reported literature to assess whether or not RLM is associated with subsequent valve degeneration or cerebrovascular events. METHODS AND RESULTS: We searched PubMed, and EMBASE (2008-2017) to identify relevant studies. Studies with <1-year follow-up, studies not evaluating RLM, and/or clinical outcomes were excluded. Our co-primary endpoints were the incidence of cerebrovascular events (stroke and/or transient ischemic attack-TIA) or structural valvular degeneration defined as moderate or greater regurgitation and/or a mean gradient ≥20 mm Hg. The literature search yielded 30 potential studies. Of these, six observational studies with a total population of 1704 patients met our selection criteria. RLM was associated with an increased risk of stroke or TIA (adjusted OR 2.60, 95% CI 1.56 to 4.34, p = 0.004). At one year, RLM was associated with an increased risk of structural valve degeneration (adjusted OR 2.51, 95% CI 1.47 to 4.30, p = 0.006). The association between RLM and clinical endpoints remained even after limiting analysis to transcatheter aortic valve replacement (TAVR) patients only. CONCLUSIONS: In patients with bio prosthetic aortic valve, presence of RLM is associated with increased risk of stroke or TIA as well as structural valvular degeneration. These findings support ongoing surveillance efforts and evaluation of pharmacotherapies to address RLM in effort to minimize subsequent clinical events.

Conduction disturbances after TAVR: Electrophysiological studies and pacemaker dependency.

BACKGROUND: Permanent pacemaker (PPM) placement occurs in 5-20% of patients after transcatheter aortic valve replacement (TAVR). Although predictors of pacemaker implantation have been established, features that predispose patients to pacemaker utilization on follow up have not been widely reported. METHODS: We performed a retrospective review of patients undergoing commercial TAVR between 2011 and 2016. We collated patients that underwent in-hospital PPM implantation and had a follow up of at least 3months. Data abstraction was performed for electrophysiological studies (EPS), pacemaker indication, timing, and device interrogation for pacemaker dependency on follow up. RESULTS: A total of 24 patients received in-hospital PPM post-TAVR (14% of total cohort), and mean follow up was 22months. Indications for PPM included resting complete heart block (CHB; 15/24, 63%), left bundle branch block and abnormal electrophysiological study (EPS; 7/24, 29%), alternating bundle branch block (1/24, 4%) and tachy-brady syndrome (1/24, 4%). Pacemaker dependency (underlying ventricular asystole, complete heart block, or >50% pacing) occurred in 8/24 patients (33%) during follow-up, 7 of whom had resting CHB, and one with CHB invoked during EPS. CONCLUSION: Pacemaker dependency after TAVR is common among those that exhibited CHB, but not among those with a prolonged HV delay during EPS. Although preliminary, these observations are relevant to management of rhythm disturbances after TAVR, and may inform the practice of EPS-based PPM implantation.

Complete Versus Incomplete Angiography Prior to Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction.

OBJECTIVES: Shorter reperfusion times in ST-elevation myocardial infarction (STEMI) are associated with improved survival. Prehospital strategies have been developed to minimize door-to-balloon (DTB) time, but few strategies within the catheterization laboratory itself have been evaluated. Incomplete angiography (IA) prior to percutaneous coronary intervention (PCI) is undertaken in clinical practice as a means to further reduce DTB time. We sought to determine whether or not those with STEMI who underwent IA prior to PCI had different preprocedural characteristics or post-PCI outcomes. METHODS: We retrospectively reviewed patients presenting to our institution between March 2013 and December 2015. Clinical, demographic, and angiographic data were reviewed. The frequency, predictors, and outcomes among those who received IA vs complete angiography (CA) prior to PCI were compared with analysis of variance. RESULTS: Two hundred fifty-six patients were identified; 68 patients (26.6%) underwent IA and 188 patients (73.4%) had CA prior to PCI. Patients who received IA were younger, but no other preprocedural factors were predictive of IA. The practice of IA did vary by operator (range, 0%-47%; P<.01). DTB times were shorter in the IA group (28.1 min vs 37.3 min; P<.01). Overall outcomes, including peak troponin values, length of stay, in-hospital mortality, and discharge ejection fraction did not differ between the groups. CONCLUSION: IA is associated with shorter DTB times, although in this population was not associated with improvements in short-term outcomes.

Vascular Assessment for Transcatheter Aortic Valve Replacement: Intravascular Ultrasound Compared With Computed Tomography.

BACKGROUND: Assessment of the femoral and iliac arteries is essential prior to transcatheter aortic valve replacement (TAVR). It is critical for establishing candidacy for a femoral approach, and can help predict vascular complications. Although computed tomography angiography (CTA) is the standard imaging modality, it has limitations. OBJECTIVE: This study compared CTA with intravascular ultrasound (IVUS) in patients undergoing TAVR evaluation. METHODS: Fifteen patients undergoing pre-TAVR coronary angiography and hemodynamic assessment were recruited. Following coronary angiography, patients underwent distal aortography, bilateral iliac and femoral arteriography, and IVUS assessment. Vascular tortuosity, minimum lumen diameter, and cross-sectional area were obtained and the findings were compared with those obtained from CTA. RESULTS: Correlation between IVUS and CTA was strong for minimum luminal diameter (r=0.62). Concordance was also strong between CTA and invasive iliofemoral angiography for assessment of tortuosity (r=0.75). Utilizing Bland-Altman analysis, vessel diameters obtained by IVUS were consistently greater than those obtained by CTA. The angiography and IVUS strategy was associated with a lower overall mean contrast utilization (29 cc vs 100 cc; P<.001), reduced mean radiation exposure (527 mGy vs 998 mGy; P=.045), and no significant difference in mean test duration (13.3 minutes vs 10 minutes; P=.12). CONCLUSIONS: For femoral and iliac arterial assessment prior to TAVR, IVUS is a viable alternative to CTA with comparable accuracy, and the potential for less contrast use and less radiation exposure. IVUS is also a valuable adjunct to CTA in patients with borderline femoral access diameters or considerable CTA artifacts.

Evaluation of Variable Thin-Cap Fibroatheroma Definitions and Association of Virtual Histology-Intravascular Ultrasound Findings With Cavity Rupture Size.

The accepted definition of virtual histology intravascular ultrasound (IVUS-VH) thin-cap fibroatheroma (TCFA) is only a modest predictor of plaque rupture (PR). We sought to determine the relation between IVUS-VH findings and culprit lesions with PR using computational analysis. A total of 80 culprit lesions from 80 patients with stable angina (n = 37), unstable angina (n = 20), and myocardial infarction (n = 23) were divided into those with (n = 15) and without PR (n = 65). By use of automated computational analysis, the standard IVUS-VH TCFA criterion and 124 additional criteria were compared. The standard TCFA definition demonstrated modest ability to discriminate lesions with and without PR (sensitivity 87%, specificity 37%, PPV 0.24, and NPV 0.92). Of 124 additional IVUS-VH TCFA definitions, only 2 improved the discriminative ability even modestly. However, a positive correlation was demonstrated between cavity size and necrotic core percentage (r = 0.78, p <0.01) and a negative correlation with percentage of fibrous tissue (r = -0.81, p <0.01). In conclusion, IVUS-VH criteria were only modestly associated with PR, without significant improvement by varying IVUS-VH TCFA features, but IVUS-VH features of ruptured plaques were strongly correlated with cavity size.

Characterization of the 2013 dengue epidemic in Myanmar with dengue virus 1 as the dominant serotype.

In 2013 in Myanmar, dengue epidemic occurred with 20,255 cases including 84 deaths. This study aimed to determine the serological and molecular characteristics of dengue virus (DENV) infection among children with clinical diagnosis of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) during this period. Single acute serum samples were collected from 300 children in Mandalay Children Hospital, Mandalay, Myanmar. Out of the 300 children, 175 (58.3%) and 183 (61%) were positive for anti-dengue IgM and anti-dengue IgG, respectively. Among the IgM positives, 41 (23.4%) had primary DENV infection. Thirty-nine DENV strains (23 DENV-1, 10 DENV-2 and 6 DENV-4) were successfully isolated after inoculation of the patient serum samples onto C6/36 cells. DENV 1 was the dominant serotype in the 2013 epidemic. There was no correlation between the infecting serotypes and clinical severities. The DENV-1 strains belonged to three lineages of the genotype 1; the DENV-2 strains were of the Asian I genotype and were separated into two lineages; and DENV-4 strains belonged to the same lineage of genotype I. It is of interest to note the diversity of DENV-1 and -2 circulating in the same location during June-August 2013. These DENV isolates were genetically close (98%-100%) to the other previously reported isolates from Myanmar and its neighboring countries, namely China, Thailand, Sri Lanka, Cambodia and Vietnam. Primary DENV infection was still high among the severe dengue cases. Different serotypes of DENV were co-circulating in 2013, however, genotype shift was not observed. Additionally, amino acid mutations were detected in the study strains not seen in the previously reported strains from other countries and Myanmar. This paper provided information on the circulating serotypes for the last 15years and the recent dengue situation in Mandalay, Myanmar after 2006.

Meta-Analysis of the Relation of Ventricular Arrhythmias to All-Cause Mortality After Implantation of a Left Ventricular Assist Device.

Ventricular arrhythmias (VAs) are commonly reported after implantation of left ventricular assist devices (LVADs). Their relation to all-cause mortality and potential risk factors remains unclear. We conducted a meta-analysis of observational studies with the primary objective of evaluating the association of post-LVAD VAs with all-cause mortality at 60, 120, and 180 days. The secondary end point was the association of potential risk factors (cause of cardiomyopathy, indication for LVAD, and history of VA) with mortality in patients with post-LVAD VAs. We searched MEDLINE, Embase, and Cochrane Central from 2001 to 2015. Two reviewers independently searched, selected, and assessed quality of included studies with differences resolved by consensus. Data were collected and analyzed using random- and fixed-effect model, as appropriate, with inverse-variance weighting. Of 2,393 studies identified, 9 observational studies were eligible including 1,179 patients with a mean follow-up of 220 days. Post-LVAD VAs were associated with increased risk of all-cause mortality after adjusting for competing risk factors at 60 days (adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.18 to 3.11, p = 0.001), 120 days (adjusted OR 1.97, 95% CI 1.01 to 3.85, p = 0.05), and 180 days (adjusted OR 2.04, 95% CI 1.01 to 4.15, p = 0.05). Using meta-regression analysis, it was found that only history of VA was a risk factor for mortality after LVAD implantation. In conclusion, post-LVAD VA is associated with an increased risk of all-cause mortality with pre-LVAD VAs acting as a risk factor. This meta-analysis, despite being only hypothesis generating, sets the stage for prospective collection of VA information in a prospective device trial or in the Interagency Registry for Mechanically Assisted Circulatory Support.

Veterans' Continued Participation in an Annual Fecal Immunochemical Test Mailing Program for Colorectal Cancer Screening.

OBJECTIVE: The objective of this study was to determine what proportion of veterans previously screened for colorectal cancer (CRC) using fecal immunochemical testing (FIT) would be willing to undergo a second round of FIT screening. METHODS: Patients in the Iowa City Veterans Affairs Health Care System (<65 years old, asymptomatic, average risk, overdue for CRC screening) who completed a mailed FIT (April 2011 to May 2012) were contacted 1 year later by telephone to collect demographic and recent CRC screening information, and were offered a second mailed FIT if eligible. RESULTS: Of 204 veterans who completed initial FIT testing, 159 were eligible to participate in a second round of FIT screening; 132 (83%) participated in the telephone survey, and 126 (79%) completed a second annual FIT, with 10 (8%) individuals testing positive. The majority of participants (67%) reported being more likely to take a yearly FIT than a colonoscopy every 10 years. Participants overwhelmingly reported that the FIT was easy to use and convenient (89%), and they were likely to complete a mailed FIT each year (97%). CONCLUSIONS: Those willing to take a mailed FIT seem satisfied with this method and willing to do it annually. Population-based or provider-based FIT mailing programs have the potential to increase CRC screening in overdue populations.

Acute coronary syndrome.

Acute coronary syndrome (ACS) is a major health care and economic burden in the United States and accounts for more than 1 million hospitalizations annually. The morbidity and mortality due to ACS are substantial-nearly half of all deaths due to coronary heart disease occur following an ACS. This review provides an up-to-date summary of the pathophysiology, diagnosis, and treatment of ACS. We also provide an overview of the management of common hemodynamic disturbances and myocardial infarction complications that physicians often encounter in an intensive care setting.

Single versus double stenting for unprotected left main coronary artery bifurcation lesions: a systematic review and meta-analysis.

OBJECTIVES: We conducted a meta-analysis to assess outcomes for a single-stent (SS) strategy versus a double-stent (DS) strategy in treatment of distal unprotected left main coronary artery (ULMCA) lesions in the drug-eluting stent (DES) era. BACKGROUND: Routine use of DES implantation has contributed to improved outcomes in patients undergoing percutaneous coronary intervention (PCI) for disease involving the ULMCA. However, PCI for ULMCA bifurcation lesions continues to be technically demanding and is an independent predictor of poor outcomes. While a number of stenting techniques have been described, the optimal strategy remains unknown. METHODS: SS treatment was defined as stenting of the main branch alone and DS treatment as stenting of both the main and side branches. Our co-primary endpoints were major adverse cardiovascular events (MACE), and its individual components. RESULTS: We identified 7 observational studies involving 2328 patients. Mean duration of follow-up was 32 months. We adopted the random effect model when computing the combined odds ratio (OR). There was decreased risk of MACE with SS strategy (20.4%) versus DS strategy (32.8%) (OR, 0.51; 95% confidence interval [CI], 0.35-0.73). There was also decreased target vessel/target lesion revascularization (TLR/TVR) with SS strategy (10.1%) versus DS strategy (24.3%) (OR, 0.35; 95% CI, 0.25-0.49). CONCLUSION: Compared to the DS strategy of percutaneous ULMCA bifurcation intervention, an SS approach may be associated with better outcomes.

Usefulness of left ventricular diastolic function to predict recurrence of atrial fibrillation in patients with preserved left ventricular systolic function.

It is unknown whether recurrence of atrial fibrillation (AF) is related to severity of left ventricular diastolic dysfunction (LVDD) before ablation in patients with preserved left ventricular ejection fraction (LVEF). We tested the hypothesis that the presence and/or severity of LVDD before catheter ablation are related to AF recurrence during the 12-month follow-up period in patients with normal LVEF. We also aimed to determine what echocardiographic and Doppler indexes of LVDD before ablation are associated with recurrence of AF after ablation. We identified 198 patients with normal LVEF who underwent catheter ablation for AF with evidence of normal sinus rhythm within 1 year before ablation. The recurrence rate during 12-month follow-up period was assessed. Of the 198 patients, 76 patients (38%) had symptomatic recurrence and 122 patients (62%) had no recurrence. None of the independent variables, including mitral valve Doppler E and A peak velocities, E/A ratio, tissue Doppler e' and a' peak velocities, left atrial volume index, isovolumic relaxation time, and deceleration time, predicted recurrence. Patients with average E/e' ratio >13, however, had increased recurrence (67% vs 35%, odds ratio 3.70, 95% confidence interval 1.21 to 11.3, p <0.05). In conclusion, there was no difference in the severity of LVDD using conventional echocardiographic indexes of LVDD in patients with or without recurrence of AF ablation. However, patients with average E/e' ratio >13 did have an increased recurrence rate of AF at 12 months after procedure. Therefore, E/e' ratio, indicative of increased left atrial pressure, may serve as a marker for AF recurrence after ablation.

Increasing colorectal cancer screening in an overdue population: participation and cost impacts of adding telephone calls to a FIT mailing program.

Many people who live in rural areas face distance barriers to colonoscopy. Our previous study demonstrated the utility of mailing fecal immunochemical tests (FIT) to average risk patients overdue for colorectal cancer (CRC screening). The aims of this study were to determine if introductory and reminder telephone calls would increase the proportion of returned FITs as well as to compare costs. Average risk patients overdue for CRC screening received a high intensity intervention (HII), which included an introductory telephone call to see if they were interested in taking a FIT prior to mailing the test out and reminder phone calls if the FIT was not returned. This HII group was compared to our previous low intensity intervention (LII) where a FIT was mailed to a similar group of veterans with no telephone contact. While a higher proportion of eligible respondents returned FITs in the LII (92 vs. 45 %), there was a much higher proportion of FITs returned out of those mailed in the HII (85 vs. 14 %). The fewer wasted FITs in the HII led to it having lower cost per FIT returned ($27.43 vs. $44.86). Given that either intervention is a feasible approach for patients overdue for CRC screening, health care providers should consider offering FITs using a home-based mailing program along with other evidence-based CRC screening options to average risk patients. Factors such as location, patient population, FIT cost and reimbursement, and personnel costs need to be considered when deciding the most effective way to implement FIT screening.

Evaluation of a home-based colorectal cancer screening intervention in a rural state.

PURPOSE: Distance from health care facilities can be a barrier to colorectal cancer (CRC) screening, especially for colonoscopy. Alternatively, an improved at-home stool-based screening tool, the fecal immunochemical test (FIT), requires only a single sample and has a better sensitivity-specificity balance compared to traditional guaiac fecal occult blood tests. Our objective was to determine if FITs mailed to asymptomatic, average-risk patients overdue for screening resulted in higher screening rates versus mailing educational materials alone or no intervention (ie, usual care). METHODS: Veterans ages 51-64, asymptomatic, at average risk for CRC, overdue for screening and in a veterans administration (VA) catchment area covering a large rural population were randomly assigned to 3 groups: (1) education only (Ed) group: mailed CRC educational materials and a survey of screening history and preferences (N = 499); (2) FIT group: mailed the FIT, plus educational materials and survey (N = 500); and (3) usual care (UC) group: received no mailings (N = 500). FINDINGS: At 6 months postintervention, 21% of the FIT group had received CRC screening by any method compared to 6% of the Ed group (and 6% of the UC group) (P < .0001). Of the 105 respondents from the FIT group, 71 (68%) were eligible to take the FIT. Of those, 64 (90%) completed the FIT and 8 (12%) tested positive. CONCLUSIONS: This low-intensity intervention of mailing FITs to average risk patients overdue for screening resulted in a significantly higher screening rate than educational materials alone or usual care, and may be of particular interest in rural areas.

Do implantable cardioverter defibrillators improve survival in patients with chronic kidney disease at high risk of sudden cardiac death? A meta-analysis of observational studies.

AIMS: Prospective randomized clinical trials show that implantable cardioverter defibrillators (ICDs) can reduce the risk of total mortality in select populations. However, data regarding patients with chronic kidney disease (CKD) are inconclusive. The aim of this study was to evaluate if ICDs affect total mortality in CKD patients at high risk of sudden cardiac death. METHODS AND RESULTS: Two separate meta-analyses were performed to (i) assess the effect of ICD on all-cause mortality in CKD patients at high risk of sudden cardiac death and (ii) assess the effect of CKD on all-cause mortality in patients who already had an ICD for primary or secondary prevention purposes. Medline and EMBASE were searched from 1966 to 2013. A manual search by cross-referencing was performed. Five observational studies with 17 460 CKD patients considered at high risk of sudden cardiac death were included to evaluate the effect of ICDs on patients with severe CKD. Patients with ICD implants had a reduction in all-cause mortality (adjusted hazard ratio (HR) = 0.65, 95% confidence interval (CI) = 0.47-0.91, P < 0.05) compared with a matched control group. Based on 15 observational studies with 5233 patients as part of our second comparison that evaluated the effect of CKD on patients who received an ICD, CKD was associated with higher mortality risk (HR = 2.86, 95% CI = 1.91-4.27, P < 0.05) despite an ICD. CONCLUSION: The meta-analysis indicates that for patients undergoing ICD implant, CKD is associated with greater risk of dying. However, ICD placement reduces mortality in CKD patients at high risk of sudden cardiac death.