Ahmed ElGuindy

Valvular aspects of rheumatic heart disease

Acute rheumatic fever and rheumatic heart disease remain major global health problems. Although strategies for primary and secondary prevention are well established, their worldwide implementation is suboptimum. In patients with advanced valvular heart disease, mechanical approaches (both percutaneous and surgical) are well described and can, for selected patients, greatly improve outcomes; however, access to centres with experienced staff is very restricted in regions that have the highest prevalence of disease. Development of diagnostic strategies that can be locally and regionally provided and improve access to expert centres for more advanced disease are urgent and, as yet, unmet clinical needs. We outline current management strategies for valvular rheumatic heart disease on the basis of either strong evidence or expert consensus, and highlight areas needing future research and development.

Taking Cardiac Surgery to the People

Cardiovascular disease (CVD) is currently the leading cause of mortality in the world, and it is estimated that 80 % of the disease burden is encountered in low- and middle-income countries (LMICs). While numerous wake-up calls have been issued in the recent years to face this emerging epidemic, little has been achieved. One particularly deficient area is cardiac surgery. This article aims to address the challenges and barriers to establishing cardiac surgery programs in LMICs and some of the existing efforts to overcome them, focusing on a center in Aswan, Egypt, as an example.

STREAM and FAST-MI – Pharmacoinvasive therapy: A continued role for fibrinolysis in the primary PCI era

Data from the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial6 and 5-year results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI)7 are evaluated for further evidence on the effectiveness and safety of a pharmacoinvasive approach for patients presenting with acute ST-segment elevation myocardial infarction (STEMI).

Heart failure with preserved ejection fraction

Abstract Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies.

Radiation in medicine: Origins, risks and aspirations

The use of radiation in medicine is now pervasive and routine. From their crude beginnings 100 years ago, diagnostic radiology, nuclear medicine and radiation therapy have all evolved into advanced techniques, and are regarded as essential tools across all branches and specialties of medicine. The inherent properties of ionizing radiation provide many benefits, but can also cause potential harm. Its use within medical practice thus involves an informed judgment regarding the risk/benefit ratio. This judgment requires not only medical knowledge, but also an understanding of radiation itself. This work provides a global perspective on radiation risks, exposure and mitigation strategies.

Validation of Noninvasive Measurement of Cardiac Output Using Inert Gas Rebreathing in a Cohort of Patients With Heart Failure and Reduced Ejection FractionCLINICAL PERSPECTIVE

Background— Cardiac output (CO) is a key indicator of cardiac function in patients with heart failure. No completely accurate method is available for measuring CO in all patients. The objective of this study was to validate CO measurement using the inert gas rebreathing (IGR) method against other noninvasive and invasive methods of CO quantification in a cohort of patients with heart failure and reduced ejection fraction. Methods and Results— The study included 97 patients with heart failure and reduced ejection fraction (age 42±15.5 years; 64 patients (65.9%) had idiopathic dilated cardiomyopathy and 21 patients (21.6%) had ischemic heart disease). Median left ventricle ejection fraction was 24% (10%–36%). Patients with atrial fibrillation were excluded. CO was measured using 4 methods (IGR, cardiac magnetic resonance imaging, cardiac catheterization, and echocardiography) and indexed to body surface area (cardiac index [CI]). All studies were performed within 48 hours. Median CI measured by IGR was 1.75, by cardiac magnetic resonance imaging was 1.82, by cardiac catheterization was 1.65, and by echo was 1.7 L·min−1·m−2. There were significant modest linear correlations between IGR-derived CI and cardiac magnetic resonance imaging–derived CI (r=0.7; P<0.001), as well as cardiac catheterization–derived CI (r=0.6; P<0.001). Using Bland–Altman analysis, the agreement between the IGR method and the other methods was as good as the agreement between any 2 other methods with each other. Conclusions— The IGR method is a simple, accurate, and reproducible noninvasive method for quantification of CO in patients with advanced heart failure. The prognostic value of this simple measurement needs to be studied prospectively.

The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research

[first paragraph of article] Atherosclerosis, obesity, and metabolic syndrome are closely linked and constitute, arguably, the most menacing three conditions to modern society. Thus urgent, concerted efforts at several levels, utilising modern tools, are required to tackle them. Translational research is a rapidly expanding branch of science, dedicated to rapid delivery of discoveries from the bench to the bedside. The growing importance of this specialty in our field is evidenced by the establishment of the International Society of Cardiovascular Translational Research and its dedicated Journal by Nabil Dib and colleagues.

An evaluation of secondary prophylaxis for rheumatic heart disease in rural Egypt

Background: Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers. Methods: A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan. Results: 29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups. Conclusion: A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences in the populations of interest will allow for more reliable data collection methodology. Application of this tool will be used to further explore barriers to prophylaxis adherence and inform the basis for the design of future KT interventions.

Culprit lesion-only versus complete revascularization in patients with STEMI: Lessons learned from PRAMI, CvLPRIT, and DANAMI-3 PRIMULTI

BACKGROUND Primary percutaneous coronary intervention (PCI) is the current standard of care for ST-elevation myocardial infarction (STEMI). About 40–50% of patients presenting with STEMI have multivessel disease (MVD). Compared to patients with single vessel disease, patients with STEMI and MVD have higher mortality rates and a greater incidence of non-fatal re-infarction. The underlying mechanism for this adverse prognosis may be plaque instability in a non-infarct vessel, impaired myocardial perfusion and contractility and/or arrhythmia. It has been shown that patients presenting with STEMI and coexisting chronic total occlusion (CTO) of a non-infarct artery have worse clinical outcomes – including higher mortality – compared to those with no concomitant CTO. It is unclear whether the poorer prognosis of patients presenting with STEMI and MVD is attributable to residual ischemia due to untreated lesions or simply due to an increased disease burden. The concept of PCI of non-culprit lesions during index hospitalization in patients undergoing primary PCI has been debated for years. Multivessel intervention during the index primary PCI has some potential advantages. It may limit the infarct size and preserve left ventricular function, as well as prevent recurrent ischemia and infarction. On the other hand, a prolonged multivessel procedure may increase contrast use and risk of stent thrombosis in non-culprit lesions given the pro-inflammatory and pro-thrombotic state associated with STEMI. Historical data provided conflicting evidence on the benefit of multivessel PCI in patients with STEMI. Previous meta-analyses showed that multivessel PCI compared with IRA-PCI resulted in worse outcomes in cohort studies. Earlier non-randomized studies showed that multivessel PCI performed during the index procedure was associated with the highest mortality whereas multivessel PCI done at a later stage – either during the index admission or within one month – was associated with the lowest mortality. Due to these uncertainties, a number of randomized trials aiming to identify the optimal management strategy of multivessel coronary artery disease in the setting of primary PCI have been conducted over the past few years.

PARADIGM-HF: Have we achieved a new paradigm in the treatment of heart failure?

PARADIGM-HF After several years of a disappointing series of negative clinical trials investigating novel therapies for systolic heart failure, the presentation of the landmark PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial at the 2014 Congress of the European Society of Cardiology in Barcelona, with simultaneous publication in the New England Journal of Medicine, 1 has created considerable excitement and optimism. With knowledge that the trial had been halted prematurely by the independent data and safety monitoring committee (DSMB), the results were eagerly anticipated, and the trial results lived up to the expectations. PARADIGM-HF investigated the impact of LCZ696 (the novel combination of an angiotensin-receptor blocker (ARB) plus the neprilysin inhibitor sacubitril) compared to the angiotensin converting enzyme (ACE) inhibitor enalapril on outcomes of 8442 patients with heart failure and left ventricular systolic dysfunction (ejection fraction 40%). ACE inhibitors have been the cornerstone of treatment for heart failure with reduced ejection fraction for over two decades and are firmly embedded in U.S. and European guidelines for the management of heart failure. 2,3 Virtually all patients in the trial were receiving ACE inhibitors or ARBs prior to enrollment but had persistent left ventricular dysfunction. The trial randomly assigned 4187 patients to receive LCZ696 200 mg twice daily and 4212 to receive enalapril 10 mg twice daily. The 200 mg dose of LCZ696 includes the ARB equivalent of 160 mg of valsartan. Background therapy included beta adrenergic receptor blockers in 93% of patients and mineralocorticoid antagonists in 56%. The primary endpoint was cardiovascular death or hospitalization for heart failure, but PARADIGM-HF was also designed as a cardiovascular mortality trial with the power to detect a 15% reduction in mortality with LCZ696 compared to enalapril, which would represent a doubling of survival benefit relative to that of current inhibitors of the renin-angiotensin system. The DSMB was allowed to halt the trial prematurely only if there was a compelling effect on cardiovascular mortality. The DSMB stopped the trial after a median follow-up period of 27 months, because of evidence of significant benefit of LCZ696, with cardiovascular mortality rates of 13.3% in the LCZ696 group and 16.5% in the enalapril group (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.71 to 0.89; P , 0.001). At the time of trial termination, 21.8% of the LCZ696 group and 26.5% of the enalapril group had reached the primary combined endpoint (HR 0.80; 95% CI, 0.73 to 0.87; P , 0.001). LCZ696 was also associated with lower overall mortality 17.0% versus 19.8%; HR 0.84; 95% CI, 0.76 to 0.93; P , 0.001), reduced risk of hospitalization (21% decrease, P , 0.001) and reduced symptomatic limitation (P ¼ 0.001). Hypotension and non-serious angioedema occurred more frequently in the LCZ696 group, but renal impairment, hyperkalemia, and cough occurred more frequently in the enalapril group.