Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Risk of Malignant Arrhythmias in Initially Symptomatic Patients With Wolff-Parkinson-White Syndrome: Results of a Prospective Long-Term Electrophysiological Follow-Up Study
- Myocardial Ischemic Events in Patients With Atrial Fibrillation Treated With Dabigatran or Warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) Trial
- Hyponatremia, Hypernatremia, and Mortality in Patients With Chronic Kidney Disease With and Without Congestive Heart Failure
- The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice
- Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation
- Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation
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Risk of Malignant Arrhythmias in Initially Symptomatic Patients With Wolff-Parkinson-White Syndrome: Results of a Prospective Long-Term Electrophysiological Follow-Up Study
Wolff-Parkinson-White syndrome decreases quality of life because of the lifetime risk of developing malignant arrhythmias and/or of dying suddenly. Specific risk factors to prevent sudden death are not yet established because no systematic long-term follow-up studies in large cohorts of patients looking at predictors of sudden death are currently available. This study presents follow-up data of 369 (23±12.5 years) untreated patients with Wolff-Parkinson-White syndrome and a first episode of supraventricular tachycardia. The results demonstrated that at 5 years most patients (>90%) did not experience recurrent arrhythmia (168 patients) or had benign recurrences (172 patients). In contrast, a malignant presentation developed in 29 patients (7%) and hemodynamic collapse or cardiac arrest resulting from ventricular fibrillation occurred in 4 patients (1.4%), confirming that, in symptomatic patients with Wolff-Parkinson-White syndrome, the risk of malignant arrhythmia and/or sudden death is low. Multivariable predictors of malignant arrhythmias were only short accessory-pathway effective refractory period (<0.001) and atrial fibrillation after atrioventricular reentrant tachycardia (<0.001). These findings provide strong evidence that electrophysiological testing is useful for identifying initially symptomatic Wolff-Parkinson-White patients at higher risk in whom catheter ablation should be performed contextually with electrophysiological testing. Liberal indications for catheter ablation may be recommended for patients at lower risk, who represent the vast majority of symptomatic patients. Our experience for the first time demonstrates that, in initially symptomatic patients with Wolff-Parkinson-White syndrome, predictors of malignant arrhythmias are the same as for asymptomatic patients. See p 661.
Myocardial Ischemic Events in Patients With Atrial Fibrillation Treated With Dabigatran or Warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) Trial
Dabigatran etexilate is a novel, potent, competitive, and reversible direct thrombin inhibitor that recently has been compared with warfarin for prevention of thromboembolic events in 18 113 patients with nonvalvular atrial fibrillation (Randomized Evaluation of Long-Term Anticoagulation Therapy [RE-LY trial]). At a dose of 110 mg twice daily, dabigatran had similar efficacy as warfarin in preventing stroke and systemic embolism but lower rates of major hemorrhage. At a dose of 150 mg twice daily, dabigatran was associated with lower rates of stroke and systemic embolism than warfarin but similar rates of major hemorrhage. This post hoc study evaluated the incidence of myocardial ischemic events, including myocardial infarction (MI), in the 3 treatment arms. MI occurred at annual rates of 0.82% and 0.81% with dabigatran 110 mg or 150 mg BID compared with 0.64% in patients taking warfarin (hazard ratio 1.29, 95% confidence interval 0.96–1.75, P=0.09 for dabigatran 110 mg; hazard ratio 1.27, 95% confidence interval 0.94–1.71, P=0.12 for dabigatran 150 mg). Events prespecified as “net clinical benefit” (all strokes, systemic embolism, MI, pulmonary embolism, major bleeding, and all-cause death) occurred at a rate of 7.34% per year with dabigatran 110 mg, 7.11% per year with dabigatran 150 mg, and 7.91% per year with warfarin (hazard ratio 0.92, 95% confidence interval 0.84–1.01, P=0.09 for dabigatran 110 mg; 0.90, 95% confidence interval 0.82–0.99, P=0.02 for dabigatran 150 mg). In conclusion, in patients with atrial fibrillation, there was a nonsignificant increase in MIs with dabigatran compared with warfarin, but other myocardial ischemic events were not increased. The net clinical benefit favors dabigatran over warfarin in patients with or without a baseline history of MI or coronary artery disease. See p 669.
Hyponatremia, Hypernatremia, and Mortality in Patients With Chronic Kidney Disease With and Without Congestive Heart Failure
We examined associations of serum sodium levels with all-cause mortality in 655 493 US veterans with chronic kidney disease, 15% of whom suffered from congestive heart failure. During a median follow-up of 5.5 years, 169 158 patients (26%) had at least 1 episode of hyponatremia, and 45 666 (7%) had at least 1 episode of hypernatremia. Both hyponatremia and hypernatremia were associated with significantly higher short-term mortality, independent of comorbidities such as congestive heart failure or liver disease. Severity of kidney disease did not affect the association of hyponatremia with mortality, but patients with more advanced chronic kidney disease appeared to tolerate hypernatremia relatively better. These observations extend the findings of earlier studies regarding the association of hyponatremia and hypernatremia with increased mortality to a patient population with chronic kidney disease, which is known to suffer from a high burden of comorbidities and a very high cardiovascular mortality rate. Even though the results of this study cannot prove that hyponatremia and hypernatremia are causes of higher mortality, they emphasize the important predictive value of serum sodium levels in patients with chronic kidney disease and establish this patient population as a potential target for future clinical trials testing interventions to correct abnormal serum sodium levels. See p 677.
The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice
Heart failure is the major serious complication of myocardial infarction. Circulating bone-marrow–derived stem cells play a critical role in repair mechanisms of infarcted myocardium and limit disease progression and heart failure. Clinical trials suggest that regenerative mechanisms of the diseased myocardium can be supported by administration of autologous bone-marrow–derived stem cells. One major limitation of the stem cell–based treatment option is low and undirected accumulation of cells with high regenerative potential at the site of injured myocardium. Bifunctional recombinant molecules that target both structures of the diseased myocardial microcirculation and distinct circulating bone-marrow–derived stem cells such as SDF1-GPVI have been shown to be of great potential to augment peripheral recruitment of stem cells toward diseased myocardium. These molecules have been proven to limit heart failure and preserve myocardium in disease-related mouse models. These molecules may be a promising strategy to promote myocardial repair and to preserve cardiac function after myocardial infarction. See p 685.
Downregulation of TMEM16A Calcium-Activated Chloride Channel Contributes to Cerebrovascular Remodeling During Hypertension by Promoting Basilar Smooth Muscle Cell Proliferation
During hypertension, cerebral arterioles undergo remodeling of the vascular walls, which contributes to the increased risk for stroke. Accumulating evidence suggests that chloride channels play an important role in regulation of cell cycle transition and cell proliferation and that the upregulation of volume-regulated chloride channel is involved in hypertension-induced cerebrovascular remodeling. Recently, TMEM16A was proposed to be the molecular candidate of the calcium-activated chloride channel (CaCC). TMEM16A has been found to be abundantly expressed and to mediate the calcium-activated chloride current in several types of vascular smooth muscle cells. However, the molecular identity of CaCC and its functions in cerebrovascular smooth muscle cells remain enigmatic. In present study, we demonstrate that TMEM16A is responsible for the CaCC in rat basilar smooth muscle cells. The activity of CaCC in basilar smooth muscle cells is remarkably reduced in hypertensive rats. Upregulation of CaMKII activity and downregulation of TMEM16A expression contribute to the attenuation of CaCC in hypertension. In addition, TMEM16A negatively regulates cell proliferation and cell cycle transition from the G0/G1 phase to the S phase through modifying cyclin D1 and cyclin E expression. These results provide evidence that the reduction of CaCC activity is an important contributor to hypertension-induced vascular smooth muscle cell proliferation and cerebrovascular remodeling, indicating that restoration of the TMEM16A CaCC activity could exert beneficial effects on hypertension-associated cardiovascular diseases such as stroke. See p 697.
Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation
Cardiac allograft vasculopathy remains the leading cause of morbidity and mortality late after heart transplantation and accounts for a third of all-cause mortality at 5 years. Traditional immunosuppression after cardiac transplantation combining calcineurin inhibitors with mycophenolate mofetil or azathioprine and corticosteroids has improved short-term survival after heart transplantation but has not prevented the development of cardiac allograft vasculopathy. Sirolimus or its derivative, everolimus, has generally been used as a secondary immunosuppressive agent in place of azathioprine or mycophenolate mofetil. Our study is the first long-term comparable serial 3-dimensional intravascular ultrasound and outcome study that demonstrates that early, and even late, conversion from calcineurin inhibitor to sirolimus as a primary immunosuppressive agent may be effective for delaying the progression of cardiac allograft vasculopathy and lumen loss. We show that sirolimus attenuates the rate of intimal hyperplasia and plaque progression in the first years after transplantation. Subsequently, it may delay the characteristic vessel remodeling biphasic response, consisting of early expansion and late constriction of vessel volume (external elastic membrane). Most important, our findings suggest that a calcineurin inhibitor–free regimen not only is safe and well tolerated but also may be effective in decreasing cardiac allograft vasculopathy–related adverse outcomes and all-cause mortality, although prospective clinical trials are required to recommend sirolimus as a first-choice primary immunosuppressant. See p 708.
- © 2012 American Heart Association, Inc.
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