Maheshwar Pauriah

Impact of Renin-Angiotensin System Blockade Therapy on Outcome in Aortic Stenosis

OBJECTIVES The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS). BACKGROUND Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling. METHODS The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations). RESULTS A total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis. CONCLUSIONS This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

More than skin deep: atherosclerosis as a systemic manifestation of psoriasis.

There is now growing evidence that psoriasis, like other inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus, is a systemic disorder that is associated with enhanced atherosclerosis and risk of coronary artery disease. Here we summarize the available epidemiological evidence for this association and analyse pathogenic features that are common to psoriasis and atherosclerosis. Further prospective studies are urgently needed to extend knowledge of the risk of cardiovascular morbidity and mortality in patients with psoriasis and to confirm the degree to which treatment of psoriasis reduces this risk. Nevertheless, existing data are sufficient to indicate that severe psoriasis should be more widely recognized as a potential risk factor for cardiovascular disease and should be considered with the established factors when formulating strategies for the management of cardiovascular risk.

The Impact of Renin-Angiotensin-Aldosterone System Blockade on Heart Failure Outcomes and Mortality in Patients Identified to Have Aortic Regurgitation : A Large Population Cohort Study

OBJECTIVES The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. METHODS The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). RESULTS A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 ± 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all-cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p < 0.01) for all-cause mortality, 0.77 (95% CI: 0.67 to 0.89; p < 0.01) for CV events, and 0.68 (95% CI: 0.54 to 0.87; p < 0.01) for AR events. CONCLUSIONS This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial.

B-type natriuretic peptide is an independent predictor of endothelial function in man.

BNP (B-type natriuretic peptide) has been reported to be elevated in preclinical states of vascular damage. To elucidate the relationship between plasma BNP and endothelial function, we have investigated the relationship between BNP and endothelial function in a cohort of subjects comprising healthy subjects as well as at-risk subjects with cardiovascular risk factors. To also clarify the relative contribution of different biological pathways to the individual variation in endothelial function, we have examined the relationship between a panel of multiple biomarkers and endothelial function. A total of 70 subjects were studied (mean age, 58.1±4.6 years; 27% had a history of hypertension and 18% had a history of hypercholesterolaemia). Endothelium-dependent vasodilatation was evaluated by the invasive ACH (acetylcholine)-induced forearm vasodilatation technique. A panel of biomarkers of biological pathways was measured: BNP, haemostatic factors PAI-1 (plasminogen-activator inhibitor 1) and tPA (tissue plasminogen activator), inflammatory markers, including cytokines [hs-CRP (high sensitive C-reactive protein), IL (interleukin)-6, IL-8, IL-18, TNFα (tumour necrosis factor α) and MPO (myeloperoxidase] and soluble adhesion molecules [E-selectin and sCD40 (soluble CD40)]. The median BNP level in the study population was 26.9 pg/ml. Multivariate regression analyses show that age, the total cholesterol/HDL (high-density lipoprotein) ratio, glucose and BNP were independent predictors of endothelial function, and BNP remained an independent predictor (P=0.009) in a binary logistic regression analysis using FBF (forearm blood flow) as a dichotomous variable based on the median value. None of the other plasma biomarkers was independently related to ACH-mediated vasodilatation. In a strategy using several biomarkers to relate to endothelial function, plasma BNP was found to be an independent predictor of endothelial function as assessed by endothelium-dependent vasodilatation in response to ACH.

High-potency statin and ezetimibe use and mortality in survivors of an acute myocardial infarction: a population-based study

Objective To determine all-cause mortality in patients with a first myocardial infarct who were treated with simvastatin compared with high-potency statin and simvastatin/ezetimibe combination. Background Despite statin use, residual cardiovascular risk remains. Therapeutic options include more potent statins or addition of ezetimibe. There is no clinical outcome data on the use of ezetimibe in such patients. Methods Retrospective longitudinal study using the United Kingdom General Practice Research Database. Patients who had survived 30 days after their first acute myocardial infarct (AMI), had not received prior statin or ezetimibe therapy and were started on a statin within 30 days of AMI were included. Three groups were identified according to their follow-up: (i) simvastatin monotherapy; (ii) high-potency statin group (patients who started on simvastatin and switched to atorvastatin or rosuvastatin); and (iii) ezetimibe/statin combination group (patients who received ezetimibe in addition to statin). Results 9597 patients (57% male, mean age of 65±13 years) matched study criteria: simvastatin (n=6990 (72.8%)); high-potency statin (n=1883, (19.6%)); and ezetimibe/statin combination (n=724 (7.5%)). During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for high-potency statin and ezetimibe group were 0.72 (95% CI 0.59 to 0.88, p<0.001) and 0.96 (95% CI 0.64 to 1.43, p=0.85), respectively. A similar result was also obtained in the propensity score analysis that took into account covariates that predicted drug treatment groups. Conclusions Patients switched to a high-potency statin had a significantly reduced mortality compared with simvastatin monotherapy. There was no observed mortality benefit in the ezetimibe group.

A stepwise approach to the management of postinfarct ventricular tachycardia using catheter ablation as the first-line treatment: a single-center experience.

Background—The occurrence of ventricular tachycardia (VT) after myocardial infarction is associated with poorer prognosis. In such patients, implantable cardioverter-defibrillators are recommended. Catheter ablation of VT is currently recommended only as an adjunctive therapy. Whether a successful VT ablation alone might be a viable strategy in some of these patients, however, remains unknown. The aim of the present study was to evaluate this strategy. Methods and Results—Between January 2002 and December 2011, 189 patients with cardiomyopathy underwent 259 VT ablations in our center. Forty-five patients (mean age, 65.2±9.6 years; 91% men) with a history of myocardial infarction and mean left ventricular ejection fraction of 39.7±9.7% matched the study criteria and were included in this analysis. Acute success was obtained in 40 of 45 patients (88.9%). During a follow-up, on the basis of our stepwise algorithm (using acute success, repeat electrophysiological study, and recurrence of VT), 19 of 45 patients (42.2%) underwent implantable cardioverter-defibrillators implantation. During a median follow-up of 4.5 (interquartile range, 2.1–7.0) years, all-cause mortality occurred in 14 of 45 patients (31.1%). Using multivariate Cox regression analysis, age (hazard ratio, 1.13; 95% confidence interval, 1.03–1.22; P=0.007) was the only independent predictor of mortality, whereas implantable cardioverter-defibrillators implantation was not (hazard ratio, 0.54; 95% confidence interval, 0.18–1.64; P=0.28) Conclusions—Our results suggest that a stepwise approach to the management of VT with ablation as a first-line treatment in postinfarct patients presenting with VT might be a reasonable option. Further studies are required to confirm these results.

Is isoproterenol really required during electrophysiological study in patients with Wolff-Parkinson-White syndrome?

UNLABELLED We have studied the results of electrophysiological study (EPS) in patients with Wolff-Parkinson-White syndrome (WPW) and spontaneous adverse clinical presentation and determined whether isoproterenol added incremental value. METHODS EPS was performed in 63 patients with WPW and adverse clinical presentation at baseline. EPS was repeated after infusion of isoproterenol in 37 patients, including 25 without criteria for a malignant form at baseline. RESULTS Atrioventricular orthodromic tachycardia was induced 44%, antidromic tachycardia in 11%, atrial fibrillation (AF) in 68% at baseline. At baseline EPS, criteria for a malignant form (AF induction and shortest CL <250 ms) were noted in 60%; tachycardia was not inducible in 16%. All the patients met the criteria for a malignant form after isoproterenol. CONCLUSIONS EPS at baseline missed 16% of patients at risk of life-threatening arrhythmias who had no inducible tachyarrhythmia and 40% without classical criteria for malignant form.

Age‐Related Prognosis of Syncope Associated with a Preexcitation Syndrome

Syncope in Wolff‐Parkinson‐White syndrome (WPW) is without relationship with WPW or reveals a poorly tolerated arrhythmia. Electrophysiologic study (EPS) is recommended. The purpose of the study was to evaluate the influence of the patients age on the causes and prognosis of syncope.

Incidence and prognostic significance of spontaneous and inducible antidromic tachycardia

AIMS Orthodromic atrioventricular reentrant tachycardia (ORT) is the most common arrhythmia at electrophysiological study (EPS) in patients with pre-excitation. The purpose of the study was to determine the clinical significance and the electrophysiological characteristics of patients with inducible antidromic tachycardia (ADT). METHODS AND RESULTS Electrophysiological study was performed in 807 patients with a pre-excitation syndrome in control state and after isoproterenol. Antidromic tachycardia was induced in 63 patients (8%). Clinical and electrophysiological data were compared with those of 744 patients without ADT. Patients with and without ADT were similar in term of age (33 ± 18 vs. 34 ± 17), male gender (68 vs. 61%), clinical presentation with spontaneous atrioventricular reentrant tachycardia (AVRT) (35 vs. 42%), atrial fibrillation (AF) (3 vs. 3%), syncope (16 vs. 12%). In patients with induced ADT, asymptomatic patients were less frequent (24 vs. 37%; <0.04), spontaneous ADT and spontaneous malignant form more frequent (8 vs. 0.5%; <0.001) (16 vs. 6%; <0.002). Left lateral accessory pathway (AP) location was more frequent (51 vs. 36%; P < 0.022), septal location less frequent (40 vs. 56%; P < 0.01). And 1/1 conduction through AP was more rapid. Orthodromic AVRT induction was as frequent (55.5 vs. 55%), but AF induction (41 vs. 24%; P < 0.002) and electrophysiological malignant form were more frequent (22 vs. 12%; P < 0.02). The follow-up was similar; four deaths and three spontaneous malignant forms occurred in patients without ADT. When population was divided based on age (<20/≥20 years), the older group was less likely to have criteria for malignant form. CONCLUSION Antidromic tachycardia induction is rare in pre-excitation syndrome and generally is associated with spontaneous or electrophysiological malignant form, but clinical outcome does not differ.

Sex-related differences in peri- and post-ablation clinical data for patients with atrial flutter

UNLABELLED Sex-related differences were not reported for the atrial flutter (AF). The purpose of the study was to look for the influence of gender on indications, clinical data and long-term results of AFl ablation. METHODS 985 patients, [227 females (23%)] were referred for radiofrequency AFl ablation. Clinical history, echocardiography were collected. Patients were followed from 3 months to 10 years. RESULTS Age of women and men was similar (65.5 ± 12 vs 64 ± 11.5 years). Underlying heart disease (HD) was as frequent in women as men (77.5 vs 77%), but women had more congenital HD (10 vs 2%;p<0.001), valvular HD (18 vs 10%;p<0.002), hypertensive HD (24 vs 18%;p<0.05), and less chronic lung disease (5 vs 10%;p<0.01), and ischemic HD (5 vs 20%;p<0.001). Atrial fibrillation (AF) history was more frequent in women (36 vs 27%;p<0.001). AFl-related tachycardiomyopathy (4.5 vs 8%;p<0.03) was more frequent, but 1/1 AFl (10 vs 6%;p=NS) as frequent. Failure of ablation (16 vs 10%;p<0.01), ablation-related major complications (3.5 vs 0.9%;p<0.005) were more frequent in women. After 3 ± 3 years, AFl recurrences were as frequent in women and men (10 vs 14%), AF occurrence more frequent in women (34 vs 19.5%; p<0.001). After excluding patients with previous AF, AF risk remained higher in women (19 vs 12%; p<0.004). CONCLUSIONS In patients admitted for ablation, AFL was less common in women than in men, despite similar age and similarly prevalent HD. More than men, women had frequent AF history, a higher risk of failure of ablation and AFl ablation-related major complications and a higher risk of AF after ablation.