Shikhar Agarwal

Updated Meta-Analysis of Septal Alcohol Ablation Versus Myectomy for Hypertrophic Cardiomyopathy

OBJECTIVES The purpose of this study was to perform a systematic review and meta-analysis of comparative studies to compare outcomes of septal ablation (SA) with septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND SM is considered the gold standard for treatment of HOCM. However, SA has emerged as an attractive therapeutic alternative. METHODS A Medline search using standard terms was conducted to determine eligible studies. Due to a lack of randomized control trials, we included observational studies for review. RESULTS Twelve studies were found eligible for review. No significant differences between short-term (risk difference [RD]: 0.01; 95% confidence interval [CI]: -0.01 to 0.03) and long-term mortality (RD: 0.02; 95% CI: -0.05 to 0.09) were found between the SA and SM groups. In addition, no significant differences could be found in terms of post-intervention functional status as well as improvement in New York Heart Association functional class, ventricular arrhythmia occurrence, re-interventions performed, and post-procedure mitral regurgitation. However, SA was found to increase the risk of right bundle branch block (RBBB) (pooled odds ratio [OR]: 56.3; 95% CI: 11.6 to 273.9) along with need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9). Although the efficacy of both SA and SM in left ventricular outflow tract gradient (LVOTG) reduction seems comparable, there is a small yet significantly higher residual LVOTG amongst the SA group patients as compared with the SM group patients. CONCLUSION SA does seem to show promise in treatment of HOCM owing to similar mortality rates as well as functional status compared with SM; however, the caveat is increased conduction abnormalities and a higher post-intervention LVOTG. The choice of treatment strategy should be made after a thorough discussion of the procedures with the individual patient.

Bariatric surgery and cardiovascular outcomes: a systematic review

Purpose To quantify the impact of bariatric surgery on cardiovascular (CV) risk factors, and on cardiac structure and function. Data sources Three major databases (PubMed, Medline and Cochrane) were searched for original studies written in English. Study selection Original articles reporting CV risk factors or non-invasive imaging parameters for patients undergoing bariatric surgery, from January 1950 to June 2012. Data extraction Data extraction from selected studies was based on protocol-defined criteria that included study design, methods, patient characteristics, surgical procedures, weight loss, changes in CV risk factors, cardiac structure and cardiac function postoperatively. Data synthesis 73 CV risk factor studies involving 19 543 subjects were included (mean age 42 years, 76% female). Baseline prevalence of hypertension, diabetes and hyperlipidaemia were 44%, 24%, and 44%, respectively. Mean follow-up was 57.8 months (range 3–176) and average excess weight loss was 54% (range 16–87%). Postoperative resolution/improvement of hypertension occurred in 63% of subjects, of diabetes in 73% and of hyperlipidaemia in 65%. Echocardiographic data from 713 subjects demonstrated statistically significant improvements in left ventricular mass, E/A ratio, and isovolumic relaxation time postoperatively. Limitations Diagnostic criteria, CV risk factor reporting, and imaging parameters were not uniform across all studies. Study groups were heterogeneous in their demographics, operative technique and follow-up period. Conclusions This systematic review highlights the benefits of bariatric surgery in reducing risk factors for CV disease. There is also evidence for left ventricular hypertrophy regression and improved diastolic function. These observations provide further evidence that bariatric surgery enhances future CV health for obese individuals.

Meta-Analysis of Transcatheter Closure Versus Medical Therapy for Patent Foramen Ovale in Prevention of Recurrent Neurological Events After Presumed Paradoxical Embolism

OBJECTIVES In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO). BACKGROUND A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO. METHODS We conducted a MEDLINE search with standard search terms to determine eligible studies. RESULTS Adjusted incidence rates of RNE were 0.8 (95% confidence interval [CI]: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia. CONCLUSIONS Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies.

Current Trial-Associated Outcomes With Warfarin in Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation: A Meta-analysis

BACKGROUND Although several new antithrombotic agents have been developed for stroke prevention in patients with nonvalvular atrial fibrillation (AF), many patients will continue to be treated with warfarin worldwide. We performed a meta-analysis of safety and efficacy outcomes in patients with AF treated with warfarin for stroke prevention in large contemporary randomized controlled trials (RCTs). METHODS We searched the MEDLINE, EMBASE, and Cochrane databases for relevant studies; RCTs comparing warfarin with an alternative thromboprophylaxis strategy with at least 400 patients in the warfarin arm and reporting stroke as an efficacy outcome were included. RESULTS Eight RCTs with 55,789 patient-years of warfarin therapy follow-up were included. Overall time spent in the therapeutic range was 55% to 68%. The annual incidence of stroke or systemic embolism in patients with AF taking warfarin was estimated to be 1.66% (95% CI, 1.41%-1.91%). Major bleeding rates varied from 1.40% to 3.40% per year across the studies. The risk of stroke per year was significantly higher in elderly patients (2.27%), female patients (2.12%), patients with a history of stroke (2.64%), and patients reporting no previous exposure to vitamin K antagonists (1.96%). There was a significant increase in the annual incidence of stroke with progressively increasing CHADS(2) (congestive heart failure, hypertension, age, diabetes, and prior stroke) scores. CONCLUSIONS Current use of warfarin as a stroke prevention agent in patients with AF is associated with a low rate of residual stroke or systemic embolism estimated to be 1.66% per year. Compared with a previous meta-analysis, there has been significant improvement in the proportion of time spent in therapeutic anticoagulation, with a resultant decline in observed stroke rates.

Long-Term Outcomes of Inoperable Patients With Aortic Stenosis Randomly Assigned to Transcatheter Aortic Valve Replacement or Standard Therapy

Background— The long-term outcomes of transcatheter aortic valve replacement (TAVR) in inoperable patients with severe aortic stenosis remain unknown. Methods and Results— In the Placement of Aortic Transcatheter Valves (PARTNER) study, 358 patients were randomly assigned to TAVR or standard therapy. We report the 3-year outcomes on these patients, and the pooled outcomes for all randomly assigned inoperable patients (n=449) in PARTNER, as well, including the randomized portion of the continued access study (n=91). The 3-year mortality rate in the TAVR and standard therapy groups was 54.1% and 80.9%, respectively (P<0.001; hazard ratio, 0.53; 95% confidence interval, 0.41–0.68; P<0.001). In survivors, there was significant improvement in New York Heart Association functional class sustained at 3 years. The cumulative incidence of strokes at 3-year follow-up was 15.7% in TAVR patients versus 5.5% in patients undergoing standard therapy (hazard ratio, 2.81; 95% confidence interval, 1.26–6.26; P=0.012); however, the composite of death or strokes was significantly lower after TAVR versus standard therapy (57.4% versus 80.9%, P<0.001; hazard ratio, 0.60; 95% confidence interval, 0.46–0.77; P<0.001). Echocardiography showed a sustained increase in aortic valve area and decrease in transvalvular gradient after TAVR. Analysis of the 449 pooled randomly assigned patients (TAVR, n=220; standard therapy, n=229) demonstrated significant improvement in all-cause mortality and functional status during early and 3-year follow-up. The results of the pooled cohort were similar to the results obtained from the pivotal PARTNER trial. Conclusions— TAVR resulted in better survival and functional status in inoperable patients with severe aortic stenosis with durable hemodynamic benefit on long-term follow-up. However, high residual mortality, even in successfully treated TAVR patients, highlights the need for more strategic patient selection. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Heavy metals and cardiovascular disease: results from the National Health and Nutrition Examination Survey (NHANES) 1999-2006.

We assessed the role of lead and cadmium as partial mediators between smoking and composite cardiovascular and cerebrovascular disease (CCVD). We also studied the association between urinary heavy metals and CCVD. Pooled data from NHANES 1999-2006 were examined. Cardiovascular and cerebrovascular disease was determined using a standardized questionnaire asking about history of stroke, angina, heart attack, coronary artery disease, and congestive heart failure. Increasing serum cadmium levels were associated with increasing prevalence of CCVD (P-trend: .03). Adjusted odds-ratio (OR) for active smokers versus never smokers was 2.09 (1.67-2.63). Adjustment for lead did not affect the OR but adjustment for cadmium significantly attenuated the OR (1.54 [1.17-2.03]). Significant association was observed between CCVD and urinary antimony, cadmium, cobalt, and tungsten. High levels of serum cadmium (>0.61 µg/L) were associated with CCVD. The relationship between smoking and CCVD was partially mediated through cadmium. Urinary antimony, cadmium, cobalt, and tungsten may be associated with CCVD.

Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement.

Background— With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results— From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P=0.2). Patients with low ejection fraction (⩽30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P<0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P<0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ⩽30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement.Background— With the availability of transcatheter aortic valve replacement, management of coronary artery disease in patients with severe aortic stenosis (AS) is posing challenges. Outcomes of percutaneous coronary intervention (PCI) in patients with severe AS and coronary artery disease remain unknown. We sought to compare the short-term outcomes of PCI in patients with and without AS. Methods and Results— From our PCI database, we identified 254 patients with severe AS who underwent PCI between 1998 and 2008. Using propensity matching, we found 508 patients without AS who underwent PCI in the same period. The primary end point of 30-day mortality after PCI was similar in patients with and without severe AS (4.3% [11 of 254] versus 4.7% [24 of 508]; hazard ratio, 0.93; 95% confidence interval, 0.51–1.69; P =0.2). Patients with low ejection fraction (≤30%) and severe AS had a higher 30-day post-PCI mortality compared with those with an ejection fraction >30% (5.4% [7 of 45] versus 1.2% [4 of 209]; P <0.001). In addition, AS patients with high Society of Thoracic Surgeons score (≥10) had a higher 30-day post-PCI mortality than those with a Society of Thoracic Surgeons score <10 (10.4% [10 of 96] versus 0%; P <0.001). Conclusions— PCI can be performed in patients with severe symptomatic AS and coronary artery disease without an increased risk of short-term mortality compared with propensity-matched patients without AS. Patients with ejection fraction ≤30% and Society of Thoracic Surgeons score ≥10% are at a highest risk of 30-day mortality after PCI. This finding has significant implications in the management of severe coronary artery disease in high-risk severe symptomatic AS patients being considered for transcatheter aortic valve replacement. # Clinical Perspective {#article-title-29}

Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients with Aortic Stenosis and Preserved Ejection Fraction

Background—We sought to assess the utility of left ventricular global longitudinal strain (LV-GLS) in predicting mortality in moderate to severe and paradoxical severe aortic stenosis (AS) patients with preserved ejection fraction. Methods and Results—We studied 395 AS patients (70±14 years, 57% men) with aortic valve area <1.3 cm2 evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction <50%). Clinical and echocardiographic data were recorded. LV-GLS was analyzed using Velocity Vector Imaging. AS patients were classified as (a) moderate–severe (n=93; aortic valve area, 1.1–1.3 cm2), (b) standard severe (n=161; aortic valve area, ⩽1 cm2; mean gradient ≥40 mm Hg), and (c) paradoxical severe (n=141; aortic valve area, ⩽1 cm2 and mean gradient <40 mm Hg). Additive Euroscore was 7±3. The association of LV-GLS with all-cause mortality was assessed after risk-adjustment using Cox proportional hazards models. Median LV-GLS was −14.8% (interquartile range, −17.2%, −12.1%). At 4.4±1.4 years, there were 92 (23%) deaths. On multivariable Cox analysis, additive Euroscore (hazard ratio, 1.19; 1.13–1.27; P<0.001), New York Heart Association class (hazard ratio, 1.44; 1.11–1.87; P<0.001), AV surgery with time-dependent covariate analysis (hazard ratio, 0.29; 0.19–0.45; P<0.001), and LV-GLS (hazard ratio, 1.05; 1.03–1.07; P<0.001) were independent predictors of mortality. LV-GLS <−12.1% (4th quartile) was associated with significantly reduced survival. Addition of LV-GLS to clinical parameters (additive Euroscore+New York Heart Association class) led to significant improvement in prediction of mortality (&khgr;2 increased from 48 to 58; P<0.01). Conclusions—LV-GLS independently predicts mortality in moderate–severe and severe AS patients with preserved LV ejection fraction, providing incremental prognostic utility, in addition to standard clinical and echocardiographic parameters.

Prognostic implications of pulmonary hypertension in patients with severe aortic stenosis

OBJECTIVE We sought to determine the clinical outcomes of patients undergoing surgical aortic valve replacement with hemodynamically confirmed severe pulmonary hypertension and aortic stenosis and compare them with the outcomes of patients not undergoing aortic valve replacement and patients undergoing aortic valve replacement with mild-to-moderate pulmonary hypertension. METHODS A total of 317 patients with severe aortic stenosis (aortic valve area < 1 cm(2)) underwent right heart catheterization along with left heart catheterization between 2004 and 2009. Severe pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg) was present in 81 patients, of whom 35 (43.2%) underwent surgical aortic valve replacement. We compared the clinical outcomes of these 35 patients with the 46 patients with severe pulmonary hypertension who did not undergo surgical aortic valve replacement. RESULTS Thirty-day mortality after aortic valve replacement was 2.85% in patients with severe pulmonary hypertension and 10.86% in patients not undergoing aortic valve replacement (P = .001). During a mean follow-up of 339.0 ± 343.7 days, overall mortality in patients undergoing aortic valve replacement was 14.2% in patients with severe pulmonary hypertension and 50% in patients with severe pulmonary hypertension who did not undergo aortic valve replacement (P < .0001). On the other hand, among patients who underwent surgery, overall mortality was similar in both the mild-to-moderate pulmonary hypertension group (23 patients [20.3%]) and the severe pulmonary hypertension group at the end of the follow-up period (P = .4). In a multivariate analysis, the presence of chronic obstructive pulmonary disease and the lack of reduction in mean pulmonary artery pressure were independent predictors of mortality in these high-risk patients undergoing aortic valve replacement, whereas baseline mean pulmonary artery pressure was not a predictor. Preoperative pulmonary capillary wedge pressure was a significant predictor of postoperative reduction in mean pulmonary artery pressure. CONCLUSIONS In patients with severe aortic stenosis and severe pulmonary hypertension who undergo aortic valve replacement, baseline pulmonary artery pressure does not unfavorably affect survival. Aortic valve replacement should be considered for patients with aortic stenosis with severe pulmonary hypertension, especially with higher pulmonary capillary wedge pressure.

Transcatheter aortic valve replacement: current perspectives and future implications

Transcatheter aortic valve replacement (TAVR) or transcatheter aortic valve implantation (TAVI) has emerged as an attractive treatment strategy for the treatment of patients with severe symptomatic aortic stenosis (AS), particularly those who are inoperable or at high risk for surgical aortic valve replacement. Several multicentre registries and randomised trials have demonstrated the safety and efficacy of this technology in improving the survival as well as functional capacity of patients with AS. Most of the elderly patients with severe AS have multiple non-cardiac comorbidities, which might limit survival and impede the improvement in functional capacity afforded by TAVR. Therefore, optimal patient selection based on precise risk assessment is currently the cornerstone of evaluation of patients for TAVR. Due to the need for a multifaceted approach in patient evaluation, procedural conduct as well as postprocedure management, multidisciplinary heart valve teams have assumed a paramount role in the TAVR process. This review presents the current perspectives in patient selection, risk assessment, procedural considerations and outcomes following TAVR, along with implications for the future.