Mohammad A Kizilbash

Comparison of mortality and morbidity in patients with atrial fibrillation and heart failure with preserved versus decreased left ventricular ejection fraction

Almost 50% of patients with congestive heart failure (HF) have preserved ejection fraction (PEF). Data on the effect of HF-PEF on atrial fibrillation outcomes are lacking. We assessed the prognostic significance of HF-PEF in an atrial fibrillation population compared to a systolic heart failure (SHF) population. A post hoc analysis of the National Heart, Lung, and Blood Institute-limited access data set of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was carried out. The patients with a history of congestive HF and a preserved ejection fraction (EF >50%) were classified as having HF-PEF (n = 320). The patients with congestive HF and a qualitatively depressed EF (EF <50%) were classified as having SHF (n = 402). Cox proportional hazards analysis was performed. The mean follow-up duration was 1,181 ± 534 days/patient. The patients with HF-PEF had lower all-cause mortality (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46 to 0.85, p = 0.003) and cardiovascular mortality (HR 0.56, 95% CI 0.38 to 0.84, p = 0.006), with a possible decreased arrhythmic end point (HR 0.39, 95% CI 0.16 to 1.006, p = 0.052) than did the patients with SHF. No differences were observed for ischemic stroke (HR 1.08, 95% CI 0.48 to 2.39, p = 0.86), rehospitalization (HR 0.89, 95% CI 0.75 to 1.07, p = 0.24), or progression to New York Heart Association class III-IV (odds ratio 0.80, 95% CI 0.42 to 1.54, p = 0.522). In conclusion, although patients with HF-PEF have better mortality outcomes than those with SHF, the morbidity appears to be similar.

Prevalence, Determinants, and Clinical Significance of Cardiac Troponin‐I Elevation in Individuals Admitted for a Hypertensive Emergency

J Clin Hypertens (Greenwich). 2011;13:551–556. ©2011 Wiley Periodicals, Inc.

Epileptic patients who survived sudden cardiac death have increased risk of recurrent arrhythmias and death

Background Cardiac arrhythmogenesis and cryptogenic epilepsy can be due to ion channel dysfunction and may coexist in the same patient. Sudden unexplained death in epilepsy (SUDEP) is a known entity with unknown cause, with the possibility of ventricular tachyarrhythmias being one of the causes. However, no prior study has investigated epileptic survivors of sudden cardiac death (SCD), recurrent life-threatening ventricular tachyarrhythmia (LTVA) and other outcomes in this patient population. Methods The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n = 1016) was a multicenter trial comparing a cardioverter-defibrillator device (ICD) (n = 507) and anti-arrhythmic drugs (AADs) (n = 499) for secondary prevention of LTVAs. Mean follow-up duration was 916 ± 471 days per patient. Patients with a history of epilepsy (n = 6) in the ICD arm were included in this analysis. End points were recurrence of LTVA, cardiac death and all-cause mortality. Results History of epilepsy (n = 6) was a significant predictor of recurrent LTVA [hazard ratio 3.53, 95% confidence interval (CI) 1.30–9.56], cardiac death (hazard ratio 4.14, 95% CI 1.30–13.14) and all-cause mortality (hazard ratio 3.82, 95% CI 1.40–10.48) in the ICD arm (n = 498). This relationship remained unchanged on multivariate analysis after controlling for baseline clinical differences. Conclusion This is the first study to investigate the effect of epilepsy on secondary prevention of LTVA. Epileptic survivors of SCD are at significantly greater risk of recurrent arrhythmias and death as compared to other survivors of recurrent LTVA. Role of coexisting channelopathies in both epilepsy and arrhythmogenesis may explain SUDEP and requires further investigation.

Valvular Perforation in Left-sided Native Valve Infective Endocarditis

Left‐sided native valve infective endocarditis (LNVIE) can result in mitral (MP) and aortic (AP) valve perforation, the prognostic significance of which remains poorly defined.

Prognostic Importance of Defibrillator Shocks in Survivors of Sudden Cardiac Death

Implantable cardioverter-de fi brillator (ICD) implantation is standard of care for patients who have survived life threatening ventricular tachyarrhythmias (LTVA). ICD shocks predict future adverse events in patients with ICD implantation for primary prevention. However, the role of ICD shocks in prediction of adverse events in a secondary prevention population is unknown. The Antiarrhythmics Versus ICDs (AVID) Trial (n=1016) was a randomized controlled trial comparing ICD (n=507) and antiarrhythmic drugs (n=509) in the treatment of patients with LTVA. Mean follow-up duration was 916 ± 471 days. We analyzed the ICD arm of the AVID trial using the NHLBI limited access dataset. ICD shocks were categorized as appropriate if underlying rhythm triggering the shock was ventricular tachycardia or ventricular fibrillation. All other ICD shocks were considered as inappropriate. Data on ICD therapy was available for 420 patients. Any shock (n=380), any appropriate (n=296) or any inappropriate (n=72) shock was not associated with increased all cause, cardiac or arrhythmic mortality. However any appropriate shock was associated with increased LTVA. In conclusion, ICD shocks do not confer increased risk of death on follow up in LTVA survivors. Use of ICD shocks as surrogate marker for adverse outcomes is not viable in secondary prevention patients.

Outcomes and Risk Prediction Model for Peripheral Arterial Disease in Patients with Stable Coronary Artery Disease

We used the National Heart, Lung, and Blood Institute Limited Access Dataset of Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) Trial (n = 8290) which included patients with stable coronary artery disease (CAD) and preserved ejection fraction (>40%). We identified risk factors for the development of critical peripheral arterial disease (PAD; those needing angioplasty, bypass grafting, or aneurysm repair) and formulated a risk score by multivariate analyses. A total of 220 patients (2.8%) developed critical PAD over a mean follow-up of 4.7 years. Significant predictors of critical PAD were history of intermittent claudication, smoking, hypertension (HTN), coronary-artery bypass grafting (CABG), diabetes, age, serum cholesterol, and body mass index (BMI). Incident critical PAD was associated with increased composite outcome of cardiovascular death, myocardial infarction, percutaneous transluminal coronary angioplasty, or CABG (hazard ratio 1.82, 95% CI 1.50-2.22, P < .001). Risk assessment using our score may identify CAD patients at risk for critical PAD events.

Combined use of direct renin inhibitor and carvedilol in heart failure with preserved systolic function

HYPOTHESES Heart failure with preserved systolic function (HFPSF) has attained epidemic proportions; however evidence-based therapeutic interventions have not advanced despite continued research over the past three decades. We propose the combined use of direct renin inhibitor and carvedilol for this condition. RATIONALE The Renin Angiotensin Aldosterone System (RAAS) plays a central role in myocyte hypertrophy, fibrosis and ventricular remodeling which is responsible for the diastolic dysfunction in HFPSF. Rising serum aldosterone levels with age have been implicated as a cause of myocardial fibrosis in the elderly. The sole use of Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers is associated with angiotensin-II and aldosterone escape and increased plasma renin activity. Carvedilol is a novel third generation non-selective β-blocker. The use of combination therapy will facilitate in better blood pressure control, reduce afterload, improve ventricular relaxation, cause regression of ventricular remodeling/fibrosis, maintain atrioventricular synchrony and enhance cardio-metabolic profile. The individual benefits of direct renin inhibitor and carvedilol could plausibly have a supra-additive effect when used in combination. Besides this, carvedilol can further reduce generation of free radicals, decrease LDL oxidation, improve Doppler echo diastolic parameters and decrease cardiac norepinephrine and density of cardiac β-receptors. CONCLUSION Evidence suggests that patients with HFPSF are treated less aggressively as compared to patients with heart failure with systolic dysfunction. Aggressive therapy with concurrent use of direct renin inhibitor and carvedilol will help in improving outcomes in this vulnerable patient sub-population. No prior trial has evaluated the combined use of these drugs for the treatment of HFPSF.

Renal disease and cardiac mortality in survivors of sudden cardiac death.

Objective - Renal disease is associated with increased all-cause mortality and cardiovascular mortality. However, the role of ICD implantation on cardiac mortality in patients with renal disease has not been well studied. Implantable cardioverter-defibrillator (ICD) implantation is protective against cardiac death in a secondary prevention population with renal disease. Methods - The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n??=??1016) was a multicentre trial comparing ICD (n = 507) and anti-arrhythmic drugs (AAD) (n = 509) for secondary prevention of life-threatening ventricular tachyarrhythmias.We performed a post-hoc analysis of the AVID trial using the National Heart, Lung, and Blood Institute limited access dataset. Individuals in the original AVID study with history of renal disease (n = 82) were included in this analysis. Outcomes of our analysis were cardiac death and all-cause mortality. Results- 41 patients had renal disease in both the ICD and AAD arms. A total of 116 patients died in the ICD arm, while 162 died in the AAD arm. Renal disease was an independent predictor (HR, 95% CI) of cardiac death (1.967, 1.09-3.57, P = 0.02) and all-cause mortality (2.04, 1.23-3.39, P = 0.01) in the AAD arm. Renal disease was also a predictor of all-cause mortality in the ICD arm (1.75, 1.01-3.01, P = 0.04). However, renal disease did not influence cardiac death in the ICD arm. Conclusions- Our study investigates the effect of ICD implantation in an entirely secondary prevention population with renal disease. ICD implantation appears to be equally protective against cardiac death in renal disease when compared to AAD.