Richard A Krasuski | Duke University School of Medicine (original) (raw)

Papers by Richard A Krasuski

Journal of the American College of Cardiology

Although GI bleeding is a known complication of LVAD implantation, its prevalence, predictors and... more Although GI bleeding is a known complication of LVAD implantation, its prevalence, predictors and outcomes remain unclear due to small and conflicting studies. Literature search was done using MEDLINE, EMBASE and Scopus from inception of these databases to June 2019 to identify all original studies

Journal of the American College of Cardiology

Journal of the American College of Cardiology

We examined a retrospective, multicenter cohort of adult Fontan patients referred for heart trans... more We examined a retrospective, multicenter cohort of adult Fontan patients referred for heart transplant (HT) to assess the impact of comorbidities and combined heart-liver transplant (CHLT) on mortality. All patients at participating institutions with a history of a Fontan-type palliation referred

Current Cardiology Reports

JAMA Network Open

IMPORTANCE Clinical researchers are obligated to present results objectively and accurately to en... more IMPORTANCE Clinical researchers are obligated to present results objectively and accurately to ensure readers are not misled. In studies in which primary end points are not statistically significant, placing a spin, defined as the manipulation of language to potentially mislead readers from the likely truth of the results, can distract the reader and lead to misinterpretation and misapplication of the findings. OBJECTIVE To determine the level and prevalence of spin in published reports of cardiovascular randomized clinical trial (RCT) reports.

Current Opinion in Lipidology

JACC: Cardiovascular Interventions

The authors sought to assess the intermediate-term effects of percutaneous placed valves in the b... more The authors sought to assess the intermediate-term effects of percutaneous placed valves in the branch pulmonary artery (PA) position. Most patients with large right ventricular outflow tracts (RVOTs) are excluded from available percutaneous pulmonary valve options. In some of these patients, percutaneous branch PA valve implantation may be feasible. The longer-term effects of valves in the branch PA position is unknown. Retrospective data were collected on patients with significant pulmonary regurgitation who had a percutaneous branch PA valve attempted. Percutaneous branch PA valve implantation was attempted in 34 patients (18 bilateral and 16 unilateral). One-half of the patients were in New York Heart Association (NHYA) functional class III or IV pre-implantation. There were 2 failed attempts and 6 procedural complications. At follow-up, only 1 patient had more than mild valvar regurgitation. The right ventricular end-diastolic volume index decreased from 147 (range: 103 to 478) ml/m to 101 (range: 76 to 429) ml/m, p < 0.01 (n = 16), and the right ventricular end-systolic volume index decreased from 88.5 (range: 41 to 387) ml/m to 55.5 (range: 40.2 to 347) ml/m, p < 0.01 (n = 13). There were 5 late deaths. At a median follow-up of 2 years, all other patients were in NYHA functional class I or II. Percutaneous branch PA valve implantation results in a reduction in right ventricular volume with clinical benefit in the intermediate term. Until percutaneous valve technology for large RVOTs is refined and more widely available, branch PA valve implantation remains an option for select patients.

Progress in Cardiovascular Diseases

Circulation. Cardiovascular quality and outcomes, 2018

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are incon... more Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I=64%). On subgroup analysis, a significant mortality reduction was seen in i...

European journal of preventive cardiology, 2018

Background The comparative effects of statins, ezetimibe with or without statins and proprotein c... more Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95%...

The American Journal of Cardiology

Current Cardiology Reports

Our review is intended to provide readers with an overview of disease processes involving the pul... more Our review is intended to provide readers with an overview of disease processes involving the pulmonic valve, highlighting recent outcome studies and guideline-based recommendations; with focus on the two most common interventions for treating pulmonic valve disease, balloon pulmonary valvuloplasty and pulmonic valve replacement. The main long-term sequelae of balloon pulmonary valvuloplasty, the gold standard treatment for pulmonic stenosis, remain pulmonic regurgitation and valvular restenosis. The balloon:annulus ratio is a major contributor to both, with high ratios resulting in greater degrees of regurgitation, and small ratios increasing risk for restenosis. Recent studies suggest that a ratio of approximately 1.2 may provide the most optimal results. Pulmonic valve replacement is currently the procedure of choice for patients with severe pulmonic regurgitation and hemodynamic sequelae or symptoms, yet it remains uncertain how it impacts long-term survival. Transcatheter pulmonic valve replacement is a rapidly evolving field and recent outcome studies suggest short and mid-term results at least equivalent to surgery. The Melody valve® was FDA approved for failing pulmonary surgical conduits in 2010 and for failing bioprosthetic surgical pulmonic valves in 2017 and has been extensively studied, whereas the Sapien XT valve®, offering larger diameters, was approved for failing pulmonary conduits in 2016 and has been less extensively studied. Patients with pulmonic valve disease deserve lifelong surveillance for complications. Transcatheter pulmonic valve replacement is a novel and attractive therapeutic option, but is currently only FDA approved for patients with failing pulmonary conduits or dysfunctional surgical bioprosthetic valves. New advances will undoubtedly increase the utilization of this rapidly expanding technology.

The American journal of cardiology, 2017

The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse out... more The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference betwe...

Pulmonary Circulation, 2017

The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high pr... more The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n ¼ 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n ¼ 18, 39%). Single group study designs were used in 44% (n ¼ 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n ¼ 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.

The American Journal of Medicine, 2016

The Journal of Invasive Cardiology, Nov 1, 2012

The role of percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic strok... more The role of percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke or transient ischemic attack remains controversial. Registry data have suggested considerable benefit of closure over medical therapy, but the prospective, randomized CLOSURE I trial found no benefit for device closure. We compared patients enrolled into CLOSURE I to off-label closures performed during the study recruitment period at a single large institution and prospectively enrolled into an institutional registry of PFO closure. We also compared CLOSURE I patients at our institution to the reported characteristics of the entire study to ensure generalizability. Between 11/3/2003 and 4/16/2007, there were 100 off-label closures and 33 patients randomized into CLOSURE I. Compared with off-label closure, patients in CLOSURE I were younger (41.6 ± 10.1 years vs 50.0 ± 14.0 years; P<.001) and had fewer cardiovascular risks including hypertension (12% vs 36%; P=.009), hyperlipidemia (24% vs 53%; P=.008), and coronary disease (3% vs 44%; P<.001). Degree of right-to-left shunting was considerably higher in off-label closures (28%, 14%, and 58% vs 45%, 30%, and 25% for mild, moderate, and severe, respectively; P=.026). Off-label closures outnumbered patient recruitment into CLOSURE 3:1 at our institution during study recruitment. Certain demographic differences were expected (age over 60 was an exclusion for CLOSURE I), but vascular risks were considerably greater in the off-label group and may be important mechanistically. Large shunts were considerably more common in off-label patients, suggesting that higher-risk patients may have been preferentially closed off-label. These results suggest that the results of CLOSURE I may not apply to all patients with initial cryptogenic stroke.

Journal of the American College of Cardiology

Although GI bleeding is a known complication of LVAD implantation, its prevalence, predictors and... more Although GI bleeding is a known complication of LVAD implantation, its prevalence, predictors and outcomes remain unclear due to small and conflicting studies. Literature search was done using MEDLINE, EMBASE and Scopus from inception of these databases to June 2019 to identify all original studies

Journal of the American College of Cardiology

Journal of the American College of Cardiology

We examined a retrospective, multicenter cohort of adult Fontan patients referred for heart trans... more We examined a retrospective, multicenter cohort of adult Fontan patients referred for heart transplant (HT) to assess the impact of comorbidities and combined heart-liver transplant (CHLT) on mortality. All patients at participating institutions with a history of a Fontan-type palliation referred

Current Cardiology Reports

JAMA Network Open

IMPORTANCE Clinical researchers are obligated to present results objectively and accurately to en... more IMPORTANCE Clinical researchers are obligated to present results objectively and accurately to ensure readers are not misled. In studies in which primary end points are not statistically significant, placing a spin, defined as the manipulation of language to potentially mislead readers from the likely truth of the results, can distract the reader and lead to misinterpretation and misapplication of the findings. OBJECTIVE To determine the level and prevalence of spin in published reports of cardiovascular randomized clinical trial (RCT) reports.

Current Opinion in Lipidology

JACC: Cardiovascular Interventions

The authors sought to assess the intermediate-term effects of percutaneous placed valves in the b... more The authors sought to assess the intermediate-term effects of percutaneous placed valves in the branch pulmonary artery (PA) position. Most patients with large right ventricular outflow tracts (RVOTs) are excluded from available percutaneous pulmonary valve options. In some of these patients, percutaneous branch PA valve implantation may be feasible. The longer-term effects of valves in the branch PA position is unknown. Retrospective data were collected on patients with significant pulmonary regurgitation who had a percutaneous branch PA valve attempted. Percutaneous branch PA valve implantation was attempted in 34 patients (18 bilateral and 16 unilateral). One-half of the patients were in New York Heart Association (NHYA) functional class III or IV pre-implantation. There were 2 failed attempts and 6 procedural complications. At follow-up, only 1 patient had more than mild valvar regurgitation. The right ventricular end-diastolic volume index decreased from 147 (range: 103 to 478) ml/m to 101 (range: 76 to 429) ml/m, p < 0.01 (n = 16), and the right ventricular end-systolic volume index decreased from 88.5 (range: 41 to 387) ml/m to 55.5 (range: 40.2 to 347) ml/m, p < 0.01 (n = 13). There were 5 late deaths. At a median follow-up of 2 years, all other patients were in NYHA functional class I or II. Percutaneous branch PA valve implantation results in a reduction in right ventricular volume with clinical benefit in the intermediate term. Until percutaneous valve technology for large RVOTs is refined and more widely available, branch PA valve implantation remains an option for select patients.

Progress in Cardiovascular Diseases

Circulation. Cardiovascular quality and outcomes, 2018

Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are incon... more Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I=64%). On subgroup analysis, a significant mortality reduction was seen in i...

European journal of preventive cardiology, 2018

Background The comparative effects of statins, ezetimibe with or without statins and proprotein c... more Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95%...

The American Journal of Cardiology

Current Cardiology Reports

Our review is intended to provide readers with an overview of disease processes involving the pul... more Our review is intended to provide readers with an overview of disease processes involving the pulmonic valve, highlighting recent outcome studies and guideline-based recommendations; with focus on the two most common interventions for treating pulmonic valve disease, balloon pulmonary valvuloplasty and pulmonic valve replacement. The main long-term sequelae of balloon pulmonary valvuloplasty, the gold standard treatment for pulmonic stenosis, remain pulmonic regurgitation and valvular restenosis. The balloon:annulus ratio is a major contributor to both, with high ratios resulting in greater degrees of regurgitation, and small ratios increasing risk for restenosis. Recent studies suggest that a ratio of approximately 1.2 may provide the most optimal results. Pulmonic valve replacement is currently the procedure of choice for patients with severe pulmonic regurgitation and hemodynamic sequelae or symptoms, yet it remains uncertain how it impacts long-term survival. Transcatheter pulmonic valve replacement is a rapidly evolving field and recent outcome studies suggest short and mid-term results at least equivalent to surgery. The Melody valve® was FDA approved for failing pulmonary surgical conduits in 2010 and for failing bioprosthetic surgical pulmonic valves in 2017 and has been extensively studied, whereas the Sapien XT valve®, offering larger diameters, was approved for failing pulmonary conduits in 2016 and has been less extensively studied. Patients with pulmonic valve disease deserve lifelong surveillance for complications. Transcatheter pulmonic valve replacement is a novel and attractive therapeutic option, but is currently only FDA approved for patients with failing pulmonary conduits or dysfunctional surgical bioprosthetic valves. New advances will undoubtedly increase the utilization of this rapidly expanding technology.

The American journal of cardiology, 2017

The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse out... more The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference betwe...

Pulmonary Circulation, 2017

The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high pr... more The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n ¼ 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n ¼ 18, 39%). Single group study designs were used in 44% (n ¼ 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n ¼ 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.

The American Journal of Medicine, 2016

The Journal of Invasive Cardiology, Nov 1, 2012

The role of percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic strok... more The role of percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke or transient ischemic attack remains controversial. Registry data have suggested considerable benefit of closure over medical therapy, but the prospective, randomized CLOSURE I trial found no benefit for device closure. We compared patients enrolled into CLOSURE I to off-label closures performed during the study recruitment period at a single large institution and prospectively enrolled into an institutional registry of PFO closure. We also compared CLOSURE I patients at our institution to the reported characteristics of the entire study to ensure generalizability. Between 11/3/2003 and 4/16/2007, there were 100 off-label closures and 33 patients randomized into CLOSURE I. Compared with off-label closure, patients in CLOSURE I were younger (41.6 ± 10.1 years vs 50.0 ± 14.0 years; P<.001) and had fewer cardiovascular risks including hypertension (12% vs 36%; P=.009), hyperlipidemia (24% vs 53%; P=.008), and coronary disease (3% vs 44%; P<.001). Degree of right-to-left shunting was considerably higher in off-label closures (28%, 14%, and 58% vs 45%, 30%, and 25% for mild, moderate, and severe, respectively; P=.026). Off-label closures outnumbered patient recruitment into CLOSURE 3:1 at our institution during study recruitment. Certain demographic differences were expected (age over 60 was an exclusion for CLOSURE I), but vascular risks were considerably greater in the off-label group and may be important mechanistically. Large shunts were considerably more common in off-label patients, suggesting that higher-risk patients may have been preferentially closed off-label. These results suggest that the results of CLOSURE I may not apply to all patients with initial cryptogenic stroke.