Mark Robbins

Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial.

CONTEXT High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. OBJECTIVE To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. DESIGN, SETTING, AND PATIENTS Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. INTERVENTIONS High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. MAIN OUTCOME MEASURES The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. RESULTS At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). CONCLUSIONS Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00645918.

Ventilatory and Heart Rate Responses to Exercise: Better Predictors of Heart Failure Mortality Than Peak Oxygen Consumption

BACKGROUND An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials.

Background—Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. Methods and Results—A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P =0.006) and 6 months (4.7% versus 2.0%, P <0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63;P <0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6% in the placebo group (odds ratio, 1.38; 95% CI, 0.85 to 2.24;P =0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72;P =0.07). Conclusions—Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Effect of Clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein

positive ST2 responses because of the design of our study. Only a few studies have addressed the diagnostic or prognostic value of ischemic ST2 occurring solely during recovery after exercise. Nearly all have used coronary angiography as the “gold standard,” and 1 had evaluation of myocardial perfusion by nongated planar Tl-201 scintigraphy. In the present study, Tc99m sestamibi was used, yielding high-quality gated SPECT images permitting quantitative assessment of perfusion, regional function, and measurement of left ventricular ejection fraction. Gianrossi et al indicated that the sensitivity of the exercise electrocardiogram for CAD detection is lower when performed in conjunction with Tl-201 scintigraphy, because ST monitoring during recovery is sacrificed for expediency in Tl-201 imaging. With perfusion imaging studies using Tc-99m, image acquisition commences approximately 30 minutes after exercise, so that the imaging protocol does not interfere with recovery ST-segment monitoring.

Renal artery end-diastolic velocity and renal artery resistance index as predictors of outcome after renal stenting

T have been numerous reports on renal angioplasty and stenting that have opposing results and opinions. Long-term hypertension may cause nephrosclerosis or glomerulosclerosis, and increase vascular resistance. Treatment of the renal artery is unlikely to improve perfusion in patients with increased microvascular resistance, and such patients are unlikely to obtain clinical benefit. Radermacher et al demonstrated that a renal artery resistance index (RI) has good predictive value in identifying patients who are unlikely to benefit from renal revascularization. In this study, we evaluated whether renal artery peak systolic (PSV) and end-diastolic (EDV) velocities and the renal artery RI can predict outcomes after renal artery stenting. • • • Patients treated for renal artery stenosis between August 2000 and February 2001 were identified from a comprehensive database of all peripheral procedures at our institution (Cleveland Clinic Foundation, Cleveland, Ohio). Seventeen patients with renal artery stenosis underwent stenting with a 100% procedural success rate (Figure 1) and underwent complete preprocedural ultrasound study. Clinical indication for renal stenting was medically refractory or difficult to treat hypertension. Clinical follow-up was systematically obtained by chart review for outpatient visit evaluation and telephone interview by physicians. All patients had a follow-up of 30 days. Renal ultrasound was performed using B-mode ultrasound guidance (ATL HDI 5000, Phillips Corporation), and a C5-2 curved array transducer (Phillips Corporation, Bothell, Washington). The PSV and the EDV were measured and the dimensionless RI was calculated as:

Impact of Renal Denervation on Patients With Obstructive Sleep Apnea and Resistant Hypertension – Insights From the SYMPLICITY HTN-3 Trial –

BACKGROUND Obstructive sleep apnea (OSA) is associated with activation of the sympathetic nervous system, and patients with this condition often experience elevated blood pressure (BP), increased BP variability, and nocturnal BP surges. METHODSANDRESULTS The SYMPLICITY HTN-3 trial was a large prospective, randomized, blinded, sham-controlled trial of renal denervation for treatment of uncontrolled, apparently treatment-resistant hypertension. In a post hoc analysis, we examined the effect of renal denervation vs. sham control on office and ambulatory (including nocturnal) systolic BP in patients with and without OSA. 26% (94/364) of renal denervation subjects and 32% (54/171) of sham control subjects had OSA. Baseline office and nighttime systolic BP values were similar in both arms, including in subjects with and without OSA. Compared with sham control, renal denervation reduced the 6-month office systolic BP in subjects with (-17.0±22.4 vs. -6.3±26.1 mmHg, P=0.01) but not in subjects without OSA (-14.7±24.5 vs. -13.4±26.4 mmHg, P=0.64), P=0.07 for the interaction between treatment arm and OSA status. In those with sleep apnea, renal denervation was also associated with a reduction in maximum (-4.8±21.8 vs. 4.5±24.6 mmHg, P=0.03) and average peak (-5.6±20.4 vs. 3.2±22.4 mmHg, P=0.02) nighttime systolic BP. CONCLUSIONS OSA subjects appeared to be responsive to renal denervation therapy. However, this hypothesis requires prospective testing. (Circ J 2016; 80: 1404-1412).

A new approach for combined carotid and coronary disease: the SHARP study.

A hybrid strategy combines the treatments traditionally available only in the catheterization laboratory (cath lab) with those traditionally available only in the operating room (OR), to offer patients the best available combination of treatments for any given set of cardiovascular lesions. Cardiac

Chest pain - A strong predictor of adverse cardiac events following percutaneous intervention (from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial [EPISTENT])

Postprocedural chest pain remains a common problem, and irrespective of electrocardiographic changes, is associated with a higher incidence of early cardiac events. A return to the catheterization laboratory is unlikely to benefit patients with postprocedural chest pain without electrocardiographic changes with documented irreversible intraprocedural complications, or those with late postprocedural pain.

Disk Embolization of a Björk-Shiley Convexo-Concave Mitral Valve: A Cause of Sudden Cardiovascular Collapse and Mesenteric Ischemia

Strut fracture and disk embolization of a Björk-Shiley convexo-concave valve is uncommon, but it should always be considered as a cause of sudden cardiovascular collapse in patients with such valves. Recognition of this clinical scenario is essential, given the importance of early diagnosis and the prevalence of these valves worldwide. We present a fatal case of disk embolization of a mitral prosthesis presenting with cardiogenic shock and mesenteric ischemia.