Advanced heart failure therapies in the Eastern Mediterranean Region: current status, challenges, and future directions.

While there has been a global decrease in rates of heart failure (HF) prevalence between 1990 and 2019, the Eastern Mediterranean region (EMR) is experiencing an increase. In 2019, approximately 1,229,766 individuals lived with moderate to severe HF in the EMR. Despite the growth in the utilization of advanced heart failure (AHF) therapies in the EMR in the past two decades, current volumes are yet to meet the growing AHF burden in the region. Heart transplantation (HT) volumes in EMR have grown from 9 in the year 2000 to 179 HTs in 2019. However, only a few centers provide the full spectrum of AHF therapies, including durable mechanical circulatory support (MCS) and HT. Published data on the utilization of left ventricular assist devices (LVAD) in the EMR are scarce. Notably, patients undergoing LVAD implantation in the EMR are on average, 13 year younger, and more likely to present with critical cardiogenic shock, as compared to their counterparts in the Western world. Furthermore, AHF care in the region is hampered by the paucity of multidisciplinary HF programs, inherent costs of AHF therapies, limited access to short and long-term MCS, organ shortage, and lack of public awareness and acceptance of AHF therapeutics. All stakeholders in the EMR should work together to strategize tackling the challenging AHF burden in the region.

Expert Recommendations to Bridge Gaps in Heart Failure Patient Support in the Middle East and Africa Region.

Heart failure (HF) remains a serious health and socioeconomic problem in the Middle East and Africa (MEA). The age-standardized prevalence rate for HF in the MEA region is higher compared to countries in Eastern Europe, Latin America, and Southeast Asia. Also cardiovascular-related deaths remain high compared to their global counterparts. Moreover, in MEA, 66% of HF readmissions are elicited by potentially preventable factors, including delay in seeking medical attention, nonadherence to HF medication, suboptimal discharge planning, inadequate follow-up, and poor social support. Patient support in the form of activation, counseling, and caregiver education has been shown to improve outcomes in patients with HF. A multidisciplinary meeting with experts from different countries across the MEA region was convened to identify the current gaps and unmet needs for patient support for HF in the region. The panel provided insights into the real-world challenges in HF patient support and contributed strategic recommendations for optimizing HF care.

Strategic Recommendations to Bridge the Gaps in Awareness, Diagnosis and Prevention of Heart Failure in the Middle East Region and Africa.

Objective: With the increasing burden of heart failure (HF) in the Middle East Region and Africa (MEA), it is imperative to shift the focus to prevention and early detection of cardiovascular diseases. We present a broad consensus of the real-world challenges and strategic recommendations for optimising HF care in the MEA region. Method: To bridge the gaps in awareness, prevention, and diagnosis of HF, an assembly of experts from MEA shared their collective opinions on the urgent unmet needs. Results: Lack of awareness in the community, high prevalence of risk factors, poor accessibility and affordability of care and diagnostics are the major barriers for delayed or missed diagnosis of HF in MEA. Enhancing patient awareness, through digital or social media campaigns, alongside raising knowledge of healthcare providers and policymakers with training programmes, can pave the way for influencing policy decisions and implementation of robust HF programmes. Multicountry registries can foster development of guidelines factoring in local challenges and roadblocks for HF care. Region-specific guidelines including simplified diagnostic algorithms can provide a blueprint of care for early detection of at-risk patients and facilitate efficient referral, thus mitigating clinician "therapeutic inertia." Multidisciplinary care teams and HF clinics with expanded role of nurses can streamline lifestyle modification and optimum control of dyslipidaemia, blood pressure, and glycaemia through guideline-recommended prevention therapies such as sodiumglucose co-transporter-2 inhibitors-thus supporting pleiotropic effects in high-risk populations. Conclusion: Development of regional guidelines, enhancing awareness, leveraging digital technology, and commitment for adequate funding and reimbursement is pivotal for overcoming structural and health system-related barriers in the MEA region.

Chronic systolic heart failure, guideline-directed medical therapy, and systemic hypotension-less pressure but maybe more risk (does this clinical scenario need more discussion?).

Many clinical trials have demonstrated the survival benefit of medication regimens that modulate the neurohormonal activation that occurs with chronic heart failure (HF). These medications, however, also commonly lower systemic blood pressure (BP). Low arterial BP in patients with chronic HF has been shown to be an independent predictor of increased mortality. Given this apparent paradox in therapeutic goals (treat aggressively but keep BP from going too low), how low should we allow systemic BP to go as a result of our medication regimens before we compromise the proven benefits of such drug therapy? Or is the association between the BP-lowering effects of standard therapy and outcomes in HF even meaningful clinically? It is from this perspective that the merits, potential clinical implications, and the relevant published literature pertaining to this patient and practice management issue will be discussed.

Comparison of the systemic levels of inflammatory markers after percutaneous coronary intervention with bare metal versus sirolimus-eluting stents.

BACKGROUND: Percutaneous coronary intervention (PCI) with bare metal stent (BMS) deployment causes plaque disruption and a rise in systemic levels of C-reactive protein (CRP), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Our aim is to study whether PCI with sirolimus-eluting stent (SES) use attenuates this response. METHODS: Patients with stable angina undergoing single-vessel PCI were enrolled in a randomized, open-label fashion into a BMS group or an SES group. Blood samples were drawn pre-PCI, 24 hours post-PCI, and 30 days post-PCI. Systemic concentrations of CRP, IL-6, and MCP-1 were measured at all time points. RESULTS: In total, 41 patients were enrolled (21 in the BMS group and 20 in the SES group). The baseline plasma concentrations of all markers were comparable between groups. At 24 hours, the mean plasma CRP concentration in the SES group was 20.21 mg/dL versus 8.95 mg/dL in the BMS group (P = 0.15). The mean plasma IL-6 concentration at 24 hours was 25.41 pg/mL in the SES group versus 17.44 pg/mL in the BMS group (P = 0.17). The mean plasma MCP-1 concentration at 24 hours was 382.38 pg/mL in the SES group versus 329.04 pg/mL in the BMS group (P = 0.2). At 30 days, plasma concentrations of all three markers decreased to similar values between groups. CONCLUSIONS: The use of SES did not inhibit the rise in systemic concentrations of CRP, IL-6, and MCP-1 at 24 hours or 30 days post-PCI, compared with BMS. Moreover, at 24 hours, there was a trend for higher systemic levels of all proinflammatory markers in the SES group compared with the BMS cohort.

Prognostic evaluation of ambulatory patients with advanced heart failure.

Previous heart failure (HF) risk models have included clinical and noninvasive variables and have been derived largely from clinical trial databases or decompensated HF registries. The importance of hemodynamic assessment is less established, particularly in ambulatory patients with advanced HF. In this study, 513 consecutive ambulatory patients (mean age 54+/-11 years, mean left ventricular ejection fraction 20+/-9%) with symptomatic HF who underwent diagnostic right-sided cardiac catheterization as part of outpatient assessment from 2000 to 2005 were reviewed. After a total of 1,696 patient-years of follow-up, 139 (27%) patients had died and 116 (23%) had undergone cardiac transplantation. The 1- and 2-year overall survival rates (defined as freedom from death or cardiac transplantation) were 77% and 67%, respectively. Overall, 65% of patients had elevated intracardiac filling pressures, and 40% had cardiac indexes<2.2 L/min/m2. In multivariate analysis, mean pulmonary arterial pressure, cardiac index, and the severity of mitral regurgitation were the 3 strongest predictors of all-cause mortality and cardiac transplantation. Renal dysfunction was also an independent predictor of all-cause mortality. When a clinical model for Cox multivariate analysis of all-cause mortality was compared with a model that also included cardiac index and mean pulmonary arterial pressure, the chi-square score increased from 45 to 69 (p<0.0001). In conclusion, in ambulatory patients with advanced HF, hemodynamic and renal function assessments remain strong independent predictors of all-cause mortality.

Prevalence of coronary artery calcium among asymptomatic men and women in a developing country: comparison with the USA data.

BACKGROUND: Coronary artery calcium score (CACS) correlates with atherosclerotic burden and predicts cardiac events. Most of the published data have been derived from the USA population. OBJECTIVE: To study the prevalence of coronary calcium in an asymptomatic population from the eastern Mediterranean region and compare it to data obtained from a large population study in the USA. RESULTS: A total of 1154 asymptomatic men and women from Lebanon underwent EBCT screening because of the presence of one or more CAD risk factors. Mean CACS as well as the percentile cut-points increased consistently with increasing age and, except for those above 74 years of age, were higher in men than women in each age stratum. Age, hypercholesterolemia, diabetes and smoking showed significant associations with CACS in men, while only age and hypercholesterolemia were significantly associated with CACS in women. Among men, the 75th and 90th percentile distributions were comparable to what is observed in developed countries such as the USA. CONCLUSION: Findings, from this first study in the region, suggest that despite a higher rate of diabetes and smokers in our study population, the CACS distribution in Lebanon is similar to that observed in the USA.

Prognostic role of pulmonary arterial capacitance in advanced heart failure.

BACKGROUND: Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. METHODS AND RESULTS: We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=-0.64) and wedge pressure (r=-0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P<0.0001) and higher PVR (P<0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84-1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s(-1)·cm(-5), P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P<0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P<0.0001). CONCLUSIONS: PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy.

Plasma myeloperoxidase concentration predicts the presence and severity of coronary disease in patients with chest pain and negative troponin-T.

BACKGROUND: A non-negligible proportion of patients with chest pain with negative cardiac troponin may harbor a disrupted coronary plaque. A marker of plaque rupture upstream from myocardial necrosis may help identify high-risk patients among this patient population. The purpose of this study was to investigate the correlation of plasma myeloperoxidase (MPO) concentration and angiographic coronary disease among patients with suspected troponin-negative coronary syndromes. PATIENTS AND METHODS: Patients presenting with chest pain and negative cardiac troponin-T concentration and undergoing coronary angiography were enrolled in our study. Plasma MPO concentration was measured using a single blood sample collected prior to cardiac catheterization. The primary angiographic endpoint was the presence of at least one coronary stenosis causing a 70% or more diameter reduction; secondary endpoints were number of diseased vessels, presence of coronary thrombus, and lesion ulceration. The main clinical endpoint was coronary revascularization. RESULTS: Three hundred and eighty-nine patients were enrolled. Presence of coronary stenosis causing a 70% or more diameter reduction increased with increasing quartiles of myeloperoxidase concentration (P<0.0001), as did the presence of coronary thrombus (P<0.0001) and plaque ulceration (P<0.0001). The need for percutaneous coronary revascularization also increased with increasing quartiles of systemic myeloperoxidase levels (P<0.0001). Coronary surgical revascularization did not differ among myeloperoxidase quartiles. CONCLUSION: Among patients with chest pain without troponin elevation, a single measurement of plasma MPO concentration can help identify patients with a higher risk of having significant coronary stenoses and high-risk angiographic features.

Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people.

The authors assessed the impact of CYP2C9*2, CYP2C9*3, and/or VKORC1-1639G>A/1173C>T single-nucleotide polymorphisms on oral anticoagulants in a Lebanese population. This study recruited 231 Lebanese participants on long-term warfarin or acenocoumarol maintenance therapy with an international normalized ratio (INR) monitored at the American University of Beirut Medical Center. CYP2C9 and VKORC1 variant alleles were screened by real-time PCR. Plasma R- and S-warfarin and R- and S-acenocoumarol levels were assayed using high-performance liquid chromatography. The variant allele frequencies of CYP2C9*2, CYP2C9*3, and VKORC1 -1639G>A/1173C>T were 15.4%, 7.8%, and 52.4%, respectively. Fifty-five participants were excluded from analysis because of nontherapeutic INR values at recruitment, leaving 43 participants taking warfarin and 133 taking acenocoumarol. There was a significant decrease in the weekly maintenance dose of both drugs with CYP2C9 and VKORC1 variants when compared with wild-type patients. CYP2C9*2 had the least impact on the response to both drugs. The concentrations of R- and S-warfarin in plasma were significantly correlated with CYP2C9 genotypes. For acenocoumarol, time to reach target INR was more prolonged in patients carrying any CYP2C9 variant allele but failed to reach statistical significance because of low numbers of patients. There was no association between allelic variants and bleeding events. This is the first pharmacogenetic study of oral anticoagulants in Arabs. The authors showed that both CYP2C9 and VKORC1 polymorphisms are common in Lebanon and influence warfarin and acenocoumarol dose requirements, with the CYP2C9*2 polymorphism having less effect on acenocoumarol, the most commonly used oral anticoagulant in Lebanon.

Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function?

OBJECTIVES: This study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF). BACKGROUND: Elevated IAP (>or=8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF. METHODS: Forty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter. RESULTS: In our study cohort (mean age 59 +/- 13 years, mean left ventricular ejection fraction 19 +/- 9%, baseline serum creatinine 2.0 +/- 0.9 mg/dl), the mean baseline IAP was 8 +/- 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable. CONCLUSIONS: Elevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable.

Sodium nitroprusside for advanced low-output heart failure.

OBJECTIVES: This study was designed to examine the safety and efficacy of sodium nitroprusside (SNP) for patients with acute decompensated heart failure (ADHF) and low-output states. BACKGROUND: Inotropic therapy has been predominantly used in the management of patients with ADHF presenting with low cardiac output. METHODS: We reviewed all consecutive patients with ADHF admitted between 2000 and 2005 with a cardiac index < or =2 l/min/m(2) for intensive medical therapy including vasoactive drugs. Administration of SNP was chosen by the attending clinician, nonrandomized, and titrated to a target mean arterial pressure of 65 to 70 mm Hg. RESULTS: Compared with control patients (n = 97), cases treated with SNP (n = 78) had significantly higher mean central venous pressure (15 vs. 13 mm Hg; p = 0.001), pulmonary capillary wedge pressure (29 vs. 24 mm Hg; p = 0.001), but similar demographics, medications, and renal function at baseline. Use of SNP was not associated with higher rates of inotropic support or worsening renal function during hospitalization. Patients treated with SNP achieved greater improvement in hemodynamic measurements during hospitalization, had higher rates of oral vasodilator prescription at discharge, and had lower rates of all-cause mortality (29% vs. 44%; odds ratio: 0.48; p = 0.005; 95% confidence interval: 0.29 to 0.80) without increase in rehospitalization rates (58% vs. 56%; p = NS). CONCLUSIONS: In patients with advanced, low-output heart failure, vasodilator therapy used in conjunction with optimal current medical therapy during hospitalization might be associated with favorable long-term clinical outcomes irrespective of inotropic support or renal dysfunction and remains an excellent therapeutic choice in hospitalized ADHF patients.

The impact of diabetes on heart failure: opportunities for intervention.

The pathophysiologic processes of diabetes mellitus and heart failure are likely interrelated. In particular, hyperglycemia and insulin resistance can induce myocardial contractile systolic and diastolic abnormalities at the cellular level. Furthermore, patients with heart failure and concomitant diabetes mellitus are more likely to have underlying comorbid conditions resulting in greater vulnerability to adverse consequences. It is reassuring that the majority of patients with diabetes mellitus and heart failure respond to standard heart failure medical regimens comparable to their nondiabetes counterparts. However, the safety profiles of current antidiabetic medications are far from ideal when used in patients with heart failure. Emerging novel therapies that reverse the metabolic and structural changes induced by the diabetic milieu are currently under clinical development, and their potential benefits may even extend beyond the diabetic population.

Noninvasive imaging in myocarditis.

Increased recognition of the role of inflammation in acute and chronic dilated cardiomyopathy has revived an interest in noninvasive imaging for detection of myocarditis. Diagnostic strategies that are based on molecular imaging promise to further advance our understanding and improve diagnostic precision. This article reviews the strengths and limitations of common clinical tests used for the diagnosis of myocarditis, with a focus on the emerging role of cardiovascular magnetic resonance imaging. Novel imaging modalities that are currently in preclinical development are discussed with recommendations for future clinical research.