Progress in cardiovascular diseases
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Prog Cardiovasc Dis · Nov 2008
ReviewRisks and challenges of implantable cardioverter-defibrillators in young adults.
The clinical use of the implantable cardioverter-defibrillator (ICD) is well established to prevent sudden death in patients with left ventricular dysfunction due to coronary artery disease and dilated cardiomyopathy, and its use has saved thousands of lives. More recently, its use has been extended to other patients at risk for sudden cardiac arrest due to ventricular fibrillation: patients with structural heart diseases such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular dysplasia and patients with normal cardiac anatomy and function except for electrophysiologic abnormalities that predispose to cardiac arrest: Brugada syndrome and long QT syndrome. A distinguishing feature of these patients may be the young age when they present for either primary or secondary prevention. ⋯ This review focuses on the unique challenges presented by device implantation in young patients 16 to 45 years of age who may have 4 to 7 decades of life with their devices. Although devices may prolong life, they come with problems that will pose unique challenges for both patients and their physicians. Moreover, because of the long durations, these problems may accelerate as patients age.
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The microcirculation is a complex system, which regulates the balance between oxygen demand and supply of parenchymal cells. In addition, the peripheral microcirculation has an important role in regulating the hemodynamics of the human body because it warrants arterial blood pressure as well as venous return to the heart. Novel techniques have made it possible that the microcirculation can be observed directly at the bedside in patients. ⋯ In human studies, the microcirculation has most extensively been investigated in septic syndromes and has revealed highly heterogeneous alterations with clear evidence of arteriolar-venular shunting. Until now, the microcirculation in acute heart failure syndromes such as cardiogenic shock has scarcely been investigated. This review concerns the physiologic properties of the microcirculation as well as its role in pathophysiologic states such as sepsis, hypovolemic shock, and acute heart failure.
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The human immunodeficiency virus (HIV) epidemic has been associated with an increase in all forms of extrapulmonary tuberculosis including tuberculous pericarditis. Tuberculosis is responsible for approximately 70% of cases of large pericardial effusion and most cases of constrictive pericarditis in developing countries, where most of the world's population live. However, in industrialized countries, tuberculosis accounts for only 4% of cases of pericardial effusion and an even smaller proportion of instances of constrictive pericarditis. ⋯ Treatment consists of 4-drug therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol) for 2 months followed by 2 drugs (isoniazid and rifampicin) for 4 months regardless of HIV status. It is uncertain whether adjunctive corticosteroids are effective in reducing mortality or pericardial constriction, and their safety in HIV-infected patients has not been established conclusively. Surgical resection of the pericardium is indicated for those with calcific constrictive pericarditis or with persistent signs of constriction after a 6 to 8 week trial of antituberculosis treatment in patients with noncalcific constrictive pericarditis.
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Cell transplantation is emerging as a new treatment designed to improve the poor outcome of patients with cardiac failure. Its rationale is that implantation of contractile cells into postinfarction scars could functionally rejuvenate these areas. Primarily for practical reasons, autologous skeletal myoblasts have been the first to be considered for a clinical use. ⋯ Furthermore, there is increasing evidence that myoblasts may act by attenuating left ventricular remodeling or paracrinally affecting the surrounding myocardium but not by generating new cardiomyocytes because of their strict commitment to a myogenic lineage. Thus, improvement of function is not tantamount of myocardial regeneration, and if such a regeneration remains the primary objective, it is worth considering alternate cell types able to generate new cardiac cells that will be electromechanically coupled with the host cardiomyocytes. In the setting of this second generation of cells, human cardiac-specified embryonic stem cells may hold the greatest promise.
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Prog Cardiovasc Dis · Jan 2007
ReviewMaking sense of noninferiority: a clinical and statistical perspective on its application to cardiovascular clinical trials.
Active control noninferiority trials are being used with increasing frequency in new drug or device development when standard placebo-controlled trials are considered unethical. Nevertheless, the design and analysis of these trials are founded on a number of assumptions and arbitrary criteria that are generally not well understood or justifiable. ⋯ When conservative criteria were applied to each of the key assumptions underlying 2 representative noninferiority trials, they materially undermined the conclusions regarding noninferiority failing to confirm reported conclusions regarding noninferiority despite enthusiastic dissemination and acceptance of the results. Because the clinical, regulatory, and economic impact of active control noninferiority trials is substantial, robust criteria should be used routinely in their design, analysis, and interpretation to reach their intended objectives and to keep them from becoming wasted efforts.