Prashant Kaul

Catheter-based renal denervation in the treatment of resistant hypertension

Clinical trials have shown that catheter-based renal denervation (RD), i.e. interruption of afferent and efferent sympathetic nerves supplying the kidney, can reduce systolic blood pressure (BP) by approximately 30 mm Hg. This technology is currently being tested as a therapeutic option for patients with resistant hypertension, a condition in which BP remains elevated despite adherence to a rational medication regimen. This novel treatment approach was developed on the basis of a wealth of animal and human research demonstrating the importance of the sympathorenal axis in the pathogenesis of hypertension. Sympathetic efferent signals to the kidneys raise BP by stimulating sodium retention and renin release, and the kidneys influence central sympathetic drive via afferent nerves. But as is true with many therapeutic advances, RD has shown benefit in clinical studies long before the mechanisms are fully understood. Additional research is needed to understand the contribution of afferent sympathetic nerve interruption to BP reductions observed with RD; to examine the degree and significance of re-innervation following RD; to elucidate factors that may lead to a lack of response to RD in some patients; to determine whether the modulation of the sympathetic nervous system via RD can have beneficial effects independent of BP reduction; and to develop methods to measure the effectiveness of RD in real time.

Association of inpatient vs outpatient onset of ST-elevation myocardial infarction with treatment and clinical outcomes.

IMPORTANCE Reperfusion times for ST-elevation myocardial infarction (STEMI) occurring in outpatients have improved significantly, but quality improvement efforts have largely ignored STEMI occurring in hospitalized patients (inpatient-onset STEMI). OBJECTIVE To define the incidence and variables associated with treatment and outcomes of patients who develop STEMI during hospitalization for conditions other than acute coronary syndromes (ACS). DESIGN, SETTING, AND PARTICIPANTS Retrospective observational analysis of STEMIs occurring between 2008 and 2011 as identified in the California State Inpatient Database. EXPOSURES STEMIs were classified as inpatient onset or outpatient onset based on present-on-admission codes. Patients who had a STEMI after being hospitalized for ACS were excluded from the analysis. MAIN OUTCOMES AND MEASURES Regression models were used to evaluate associations among location of onset of STEMI, resource utilization, and outcomes. Adjustments were made for patient age, sex, comorbidities, and hospital characteristics. The analysis allowed for the location of inpatient STEMI to have a multiplicative rather than an additive effect for resource utilization since these measures were highly skewed. RESULTS A total of 62,021 STEMIs were identified in 303 hospitals, of which 3068 (4.9%) occurred in patients hospitalized for non-ACS indications. Patients with inpatient-onset STEMI were older (mean, 71.5 [SD, 13.5] years vs 64.9 [SD, 14.1] years; P < .001) and more frequently female (47.4% vs 32%; P < .001) than those with outpatient-onset STEMI. Patients with inpatient-onset STEMI had higher in-hospital mortality (33.6% vs 9.2%; adjusted odds ratio (AOR), 3.05; 95% CI, 2.76-3.38; P < .001), were less likely to be discharged home (33.7% vs 69.4%; AOR, 0.38; 95% CI, 0.34-0.42; P < .001), and were less likely to undergo cardiac catheterization (33.8% vs 77.8%; AOR, 0.19; 95% CI, 0.16-0.21; P < .001) or percutaneous coronary intervention (21.6% vs 65%; AOR, 0.23; 95% CI, 0.21-0.26; P < .001). Length of stay and inpatient charges were higher for inpatient-onset STEMI (mean length of stay, 13.4 days [95% CI, 12.8-14.0 days] vs 4.7 days [95% CI, 4.6-4.8 days]; adjusted multiplicative effect, 2.51; 95% CI, 2.35-2.69; P < .001; mean inpatient charges,

Atherosclerosis imaging: prognostically useful or merely more of what we know?

245,000 [95% CI,

Use of outcome measures in pulmonary hypertension clinical trials.

235,300-

Intra-Coronary Imaging Modalities

254,800] vs

Predictors, treatment, and outcomes of STEMI occurring in hospitalized patients

129,000 [95% CI,

TransRadial Education And Therapeutics (TREAT): Shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention: A report from the Cardiac Safety Research Consortium

127,900-

Management of Percutaneous Coronary Intervention Complications

130,100]; adjusted multiplicative effect, 2.09; 95% CI, 1.93-2.28; P < .001). CONCLUSIONS AND RELEVANCE Patients who had a STEMI while hospitalized for a non-ACS condition, compared with those with onset of STEMI as an outpatient, were less likely to undergo invasive testing or intervention and had a higher in-hospital mortality rate.

Angiographic severity does not correlate with fractional flow reserve in heavily calcified coronary arteries

Despite the epidemiological insights from the Framingham Study1 in the early 1950s and the resulting significant advances in the diagnosis and management of coronary heart disease (CHD), it remains the leading cause of death in the United States. In part, this is because sudden cardiac death is the first presentation of CHD in 50% of men and 64% of women2,3 and, therefore, the only available strategy for reducing mortality in these patients is primary prevention. This is the target population for atherosclerosis imaging, which has been proposed as a strategy for the earlier and more accurate identification of individuals at risk for CHD so that lifesaving preventive strategies can be more optimally targeted in those at risk. Current guidelines for primary prevention recommend initial assessment and risk stratification based on traditional risk factors (eg, the Framingham Risk Score [FRS] in the United States and the Systemic Coronary Risk Evaluation in Europe), followed by goal-directed therapy as necessary to modify those risk factors.4 However, these traditional prevention strategies can be inadequate, as cardiovascular events do occur in patients without known risk or in low and intermediate risk groups in whom an aggressive treatment strategy would not be indicated. This is highlighted by a study of 222 young adults (men ≤55 years and women ≤65 years) without known prior CHD, hospitalized for acute myocardial infarction, of whom 70% were in a low-risk category with a 10-year risk of CHD<10% based on their FRS.5 Furthermore, when the 10-year risk of these patients was stratified by number of risk factors and low-density lipoprotein cholesterol level, three quarters did not meet National Cholesterol Education Program III criteria6 to be identified as at sufficient risk to qualify for cholesterol lowering therapy. Part of the reason why FRS fails to detect risk …

In-Hospital ST-Segment Elevation Myocardial Infarction: Improving Diagnosis, Triage, and Treatment

OBJECTIVES To evaluate the use of surrogate measures in pulmonary hypertension (PH) clinical trials and how it relates to clinical practice. BACKGROUND Studies of pulmonary arterial hypertension (PAH) employ a variety of surrogate measures in addition to clinical events because of a small patient population, participant burden, and costs. The use of these measures in PH drug trials is poorly defined. METHODS We searched PubMed/MEDLINE/Embase for randomized or prospective cohort PAH clinical treatment trials from 1985 to 2013. Extracted data included intervention, trial duration, study design, patient characteristics, and primary and secondary outcome measures. To compare with clinical practice, we assessed the use of surrogate measures in a clinical sample of patients on PH medications at Duke University Medical Center between 2003 and 2014. RESULTS Between 1985 and 2013, 126 PAH trials were identified and analyzed. Surrogate measures served as primary endpoints in 119 trials (94.0%). Inclusion of invasive hemodynamics decreased over time (78.6%, 75.0%, 52.2%; P for trend = .02), while functional testing (7.1%, 60.0%, 81.5%; P for trend < .0001) and functional status or quality of life (0%, 47.6%, 62.8%; P for trend < .0001) increased in PAH trials over the same time periods. Echocardiography data were reported as a primary or secondary outcome in 32 trials (25.4%) with increased use from 1985-1994 to 1995-2004 (7.1% vs 35.0%, P = .04), but the trend did not continue to 2005-2013 (25.0%). In comparison, among 450 patients on PAH therapies at our institution between 2003 and 2013, clinical assessments regularly incorporated serial echocardiography and 6-minute walk distance tests (92% and 95% of patients, respectively) and repeat measurement of invasive hemodynamics (46% of patients). CONCLUSIONS The majority of PAH trials have utilized surrogate measures as primary endpoints. The use of these surrogate endpoints has evolved significantly over time with increasing use of patient-centered endpoints and decreasing or stable use of imaging and invasive measures. In contrast, imaging and invasive measures are commonly used in contemporary clinical practice. Further research is needed to validate and standardize currently used measures.