Project description:Nearly 40% of patients presenting to the catheter laboratory with angina have non-obstructed coronary arteries (ANOCA), an umbrella term that encompasses distinct pathophysiological entities, such as coronary artery spasm. Coronary artery spasm leads to sudden reversible coronary flow attenuation, which clinically manifests as vasospastic angina (VSA). VSA is associated with poor quality of life and an increased risk of major adverse cardiac events. However, the pathophysiological mechanisms underlying this phenomenon are incompletely understood, which has resulted in limited therapeutic options for patients afflicted with this condition. The past decade has seen a surge in new research being conducted in the field of ANOCA and VSA. This review article provides a comprehensive summary of the underlying pathophysiological mechanisms of VSA and the current therapeutic options. We also appraise the current diagnostic approach in patients with suspected VSA.
Project description:Refractory angina (RA) is defined as chest pain caused by coronary ischemia in patients on maximal medical therapy and is not amenable to revascularization despite advanced coronary artery disease (CAD). The long-term prognosis has improved with optimal medical therapy including risk factor modification. Still, patients are left with major impairment in quality of life and have high resource utilization with limited treatment options. We review the novel invasive and noninvasive therapies under investigation for RA.
Project description:Recognition of suspected ischaemia with no obstructive coronary artery disease - termed INOCA - has increased over the past decades, with a key contributor being microvascular angina. Patients with microvascular angina are at higher risk for major adverse cardiac events including MI, stroke, heart failure with preserved ejection fraction and death but to date there are no clear evidence-based guidelines for diagnosis and treatment. Recently, the Coronary Vasomotion Disorders International Study Group proposed standardised criteria for diagnosis of microvascular angina using invasive and non-invasive approaches. The management strategy for remains empirical, largely due to the lack of high-levelevidence- based guidelines and clinical trials. In this review, the authors will illustrate the updated approach to diagnosis of microvascular angina and address evidence-based pharmacological and non-pharmacological treatments for patients with the condition.
Project description:Chronic heart failure (CHF) remains the only cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditures. The prevalence of CHF increases with advancing life span, with diastolic heart failure predominating in the elderly population. Primary prevention of coronary artery disease and risk factor management via aggressive blood pressure control are central in preventing new occurrences of left ventricular dysfunction. Optimal therapy for CHF involves identification and correction of potentially reversible precipitants, target-dose titration of medical therapy, and management of hospitalizations for decompensation. The etiological phenotype, absolute decrease in left ventricular ejection fraction and a widening of QRS duration on electrocardiography, is commonly used to identify patients at increased risk of progression of heart failure and sudden death who may benefit from prophylactic implantable cardioverter-defibrillator placement with or without cardiac resynchronization therapy. Patients who transition to advanced stages of disease despite optimal traditional medical and device therapy may be candidates for hemodynamically directed approaches such as a left ventricular assist device; in selected cases, listing for cardiac transplant may be warranted.
Project description:With improvements in survival from coronary artery disease (CAD) and an ageing population, refractory angina (RA) is becoming an increasingly common clinical problem facing clinicians in routine clinical practice. These patients experience chronic symptoms in the context of CAD, characterised by angina-type pain, which is uncontrolled despite optimal pharmacological, interventional and surgical therapy. Although mortality rates are no worse in this cohort, patients experience a significantly impaired quality of life with disproportionately high utilisation of healthcare services. It has been increasingly recognised that the needs of RA patients are multifactorial and best provided by specialist multi-disciplinary units. In this review, we consider the variety of therapies available to clinicians in the management of RA and discuss the promise of novel treatments.
Project description:Pulmonary arterial hypertension (PAH) is characterized by severe remodeling of the distal pulmonary arteries, increased pulmonary vascular resistance, and right ventricular dysfunction that promotes heart failure. Once regarded as largely untreatable, evidence-based decision making now guides clinical management of PAH and improves outcomes. However, misconceptions regarding the approach to PAH in the modern era are common and associated with substandard clinical care.The clinical profile of PAH has changed substantially since its original description. Patients are older at diagnosis than previously reported; disease severity appears greater in men compared with women; and patients with PAH in association with connective tissue disease are identified as a particularly high-risk subgroup. Risk stratification scales for PAH are now available at point of care, which inform treatment goals, including a 6-minute walk distance of greater than 440 m, peak volume of oxygen consumption of greater than 15 mL/min/kg, right atrial area of less than 18 cm2, cardiac index of greater than 2.5 L/min/m2, and absent or low symptom burden with routine physical activity. At present, 14 therapies targeting 6 PAH-specific molecular intermediaries are used clinically. Recent landmark trial data have demonstrated the critical importance of initial combination therapy in treatment-naive patients. These findings underscore a global shift in PAH that couples early disease detection with aggressive pharmacotherapy. Indeed, recent longitudinal data from patients receiving combination therapy show that the 3-year survival rate in PAH may be as high as 84% compared with 48% from the original National Institutes of Health registry on idiopathic PAH (1980-1985). Despite these gains, incomplete clinical evaluation and misdiagnosis by referring clinicians is common and associated with inappropriate therapy.Compared with the original clinical experience, PAH has evolved into a contemporary and treatable disease characterized by improved survival and a high standard for defining therapeutic success. However, underawareness among clinicians regarding the importance of early and accurate PAH diagnosis persists and is a potentially reversible cause of adverse outcome in this disease.
Project description:Microvascular angina (MVA), historically called cardiac syndrome X, refers to angina with nonobstructive coronary artery disease. This female-predominant cardiovascular disorder adds considerable health-related costs due to repeated diagnostic angiography and frequent hospital admissions. Despite the high prevalence of this diagnosis in patients undergoing coronary angiography, it is still a therapeutic challenge for cardiologists. Unlike obstructive coronary artery disease, with multiple evidence-based therapies and management guidelines, little is known regarding the management of MVA. During the last decade, many therapeutic interventions have been suggested for the treatment of MVA. However, there is a lack of summarization tab and update of current knowledge about pharmacologic management of MVA, mostly due to unclear pathophysiology. In this article, we have reviewed the underlying mechanisms of MVA and the outcomes of various medications in patients with this disease. Contrary to vasospastic angina in which normal angiogram is observed as well, nitrates are not effective in the treatment of MVA. Beta-blockers and calcium channel blockers have the strongest evidence of improving the symptoms. Moreover, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, estrogen, and novel antianginal drugs has had promising outcomes. Investigations are still ongoing for vitamin D, omega-3, incretins, and n-acetyl cysteine, which have resulted in beneficial initial outcomes. We believe that the employment of the available results and results of the future large-scale trials into cardiac care guidelines would help reduce the global cost of cardiac care tremendously.
Project description:BackgroundIn patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD).ObjectivesThe goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography.MethodsFifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements.ResultsIn patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value.ConclusionsIn angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation.
Project description:The treatment of infected mandibular fractures has advanced rather dramatically over the past 50 years. Immobilization with maxillomandibular fixation and/or splints, removal of diseased teeth in the fracture line, external fixation, use of antibiotics, debridement, and rigid internal fixation has played a role in management. Perhaps the most important advance was the realization that infected fractures also result from moving fragments and nonvital bone, not just bacteria. Controlling movement and eliminating the dead bone allowed body defenses to also eliminate bacteria. The next logical step in the evolution of treatment was primary bone grafting of the resulting defect following application of rigid internal fixation and debridement of the dead bone. We offer our results with this treatment in 21 infected fractures, 20 of which achieved primary union.
Project description:High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.