Usefulness of hypertensive blood pressure response during a single-stage exercise test to predict long-term outcome in patients with peripheral arterial disease

The prognostic value of a hypertensive blood pressure (BP) response is still unclear. Therefore, the prognostic value of a hypertensive BP response in patients during single-stage exercise testing for peripheral arterial disease (PAD) on long-term mortality and major adverse cerebrovascular and cardiac events (MACCEs) was investigated. In addition, effects of statin, beta-blocker, and aspirin use in patients with known or suspected PAD were studied. A total of 2,109 patients were enrolled in an observational prospective study from 1993 to 2005. Hypertensive BP response was defined as an increase in systolic BP >/=55 mm Hg (95(th) percentile within our population) after a single-stage treadmill exercise test. The outcome was obtained by using the civil registries, and a questionnaire about cardiac events was sent to all survivals. Hypertensive BP response was associated with increased risk of long-term mortality (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12 to 1.80) and MACCEs (HR 1.47, 95% CI 1.09 to 1.97). After adjustments for clinical risk factors and propensity score, baseline statin use was associated with reduced risk of long-term mortality (HR 0.59, 95% CI 0.44 to 0.79), and statin, beta-blocker, and aspirin use were associated with reduced risk of MACCEs (HR 0.59, 95% CI 0.43 to 0.81; HR 0.75, 95% CI 0.60 to 0.95; HR 0.73, 95% CI, 0.57 to 0.92, respectively). In conclusion, hypertensive BP response at exercise in patients with known or suspected PAD is an important independent risk factor for all-cause long-term mortality and MACCEs, whereas statin, beta-blocker, and aspirin use were associated with an improved outcome.     

The potential of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes.

Patients with diabetes, in particular patients with type 2 diabetes, are at a 2- to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic peers. Patients with diabetes are also more likely to have silent ischemia and less likely to survive a myocardial infarction than nondiabetic patients. Recent studies with electron beam computed tomography (EBCT) have shown that subclinical atherosclerosis is common in patients with diabetes, and studies with myocardial perfusion scintigraphy (with single-photon emission computed tomography) or stress echocardiography have demonstrated that between 25% and 50% of asymptomatic diabetic patients have ischemia during exercise or pharmacological stress and that a substantial proportion of these patients go on to develop major cardiovascular events within several years. Clearly, asymptomatic diabetic patients include a subset of individuals at high risk of cardiovascular disease who would benefit from improved risk stratification beyond that possible with risk factor scoring systems alone. Single-photon emission computed tomography, stress echocardiography, and possibly EBCT or multi-slice computed tomography, are emerging as valuable diagnostic tools for identifying asymptomatic diabetic patients who might require early and aggressive intervention to manage their cardiovascular risk.     

Association between serum uric acid and perioperative and late cardiovascular outcome in patients with suspected or definite coronary artery disease undergoing elective vascular surgery

The role of uric acid as an independent marker of cardiovascular risk is unclear. Therefore, our aim was to assess the independent contribution of preoperative serum uric acid levels to the risk of 30-day and late mortality and major adverse cardiac event (MACE) in patients scheduled for open vascular surgery. In total, 936 patients (76% male, age 68 +/- 11 years) were enrolled. Hyperuricemia was defined as serum uric acid >0.42 mmol/l for men and >0.36 mmol/l for women, as defined by large epidemiological studies. Outcome measures were 30-day and late mortality and MACE (cardiac death or myocardial infarction). Multivariable logistic and Cox regression analysis were used, adjusting for age, gender, and all cardiac risk factors. Data are presented as odds ratios or hazard ratios, with 95% confidence intervals. Hyperuricemia was present in 299 patients (32%). The presence of hyperuricemia was associated with heart failure, chronic kidney disease, and the use of diuretics. Perioperatively, 46 patients (5%) died and 61 patients (7%) experienced a MACE. Mean follow-up was 3.7 years (range: 0 to 17 years). During follow-up, 282 patients (30%) died and 170 patients (18%) experienced a MACE. After adjustment for all clinical risk factors, the presence of hyperuricemia was not significantly associated with an increased risk of 30-day mortality or MACE, odds ratios of 1.5 (0.8 to 2.8) and 1.7 (0.9 to 3.0), respectively. However, the presence of hyperuricemia was associated with an increased risk of late mortality and MACE, with hazard ratios of 1.4 (1.1 to 1.7) and 1.7 (1.3 to 2.3), respectively. In conclusion, the presence of preoperative hyperuricemia in vascular patients is a significant predictor of late mortality and MACE.     

Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and the Programmed Death Receptor 1 (PD-1) are immune checkpoint molecules that are well-established targets of antibody immunotherapies for the management of malignant melanoma. The monoclonal antibodies, Ipilimumab, Pembrolizumab, and Nivolumab, designed to interfere with T cell inhibitory signals to activate immune responses against tumors, were originally approved as monotherapy. Treatment with a combination of immune checkpoint inhibitors may improve outcomes compared to monotherapy in certain patient groups and these clinical benefits may be derived from unique immune mechanisms of action. However, treatment with checkpoint inhibitor combinations also present significant clinical challenges and increased rates of immune-related adverse events. In this review, we discuss the potential mechanisms attributed to single and combined checkpoint inhibitor immunotherapies and clinical experience with their use.     

Assessment of left ventricular dyssynchrony in patients with conduction delay and idiopathic dilated cardiomyopathy: head-to-head comparison between tissue doppler imaging and velocity-encoded magnetic resonance imaging.

OBJECTIVES: This study sought to compare tissue Doppler imaging (TDI) with velocity-encoded (VE) magnetic resonance imaging (MRI) for left ventricular (LV) dyssynchrony assessment. BACKGROUND: Cardiac resynchronization therapy (CRT) is proposed for patients with heart failure, depressed LV function, and a wide QRS complex. Selection is based mainly on electrocardiogram criteria, but recent data suggest that intraventricular dyssynchrony may be preferred for selection. An LV dyssynchrony can adequately be assessed with TDI, but this has not been compared directly with other imaging modalities. A VE MRI potentially allows direct myocardial wall motion measurements similar to TDI. METHODS: Twenty patients with heart failure, systolic LV dysfunction, and a wide QRS complex were included, as well as 10 normal individuals with normal QRS duration and LV function. The TDI and VE MRI data were acquired to study intraventricular dyssynchrony. RESULTS: Left ventricular dyssynchrony was not observed in normal individuals (mean dyssynchrony -2 +/- 15 ms on TDI; mean -5 +/- 17 ms on MRI, p = NS). In patients, mean LV dyssynchrony was 55 +/- 37 ms on TDI; 49 +/- 38 ms on MRI (p = NS). Good correlation between both modalities was observed (linear regression TDI = 0.99 x MRI - 5, n = 30, r = 0.98, p < 0.01). The MRI showed a small, nonsignificant underestimation of 5 +/- 8 ms compared with TDI. Agreement between MRI and TDI for classification according to severity of LV dyssynchrony (minimal, intermediate, and extensive) was excellent (kappa +/- SE = 0.96 +/- 0.07, p < 0.01) with 95% of patients classified identical. CONCLUSIONS: Both MRI and TDI yield comparable information on LV dyssynchrony; MRI is useful in the selection of patients for CRT.     

Cardiac resynchronization therapy in patients with a narrow QRS complex.

OBJECTIVES: The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (<120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI). BACKGROUND: Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (> or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied. METHODS: Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchrony > or =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fraction < or =35%. RESULTS: Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]). CONCLUSIONS: Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.