SARS-CoV 2 Infection (Covid-19) and Cardiovascular Disease in Africa: Health Care and Socio-Economic Implications.

The current pandemic of SARS-COV 2 infection (Covid-19) is challenging health systems and communities worldwide. At the individual level, the main biological system involved in Covid-19 is the respiratory system. Respiratory complications range from mild flu-like illness symptoms to a fatal respiratory distress syndrome or a severe and fulminant pneumonia. Critically, the presence of a pre-existing cardiovascular disease or its risk factors, such as hypertension or type II diabetes mellitus, increases the chance of having severe complications (including death) if infected by the virus. In addition, the infection can worsen an existing cardiovascular disease or precipitate new ones. This paper presents a contemporary review of cardiovascular complications of Covid-19. It also specifically examines the impact of the disease on those already vulnerable and on the poorly resourced health systems of Africa as well as the potential broader consequences on the socio-economic health of this region.

Assessment of patients presenting with life-threatening ventricular arrhythmias and suspected myocarditis: The key role of endomyocardial biopsy.

BACKGROUND: Life-threatening ventricular tachyarrhythmias (VAs) represent a significant cause of death in myocarditis. OBJECTIVE: The purpose of this study was to identify predictors of sustained VAs in patients with myocarditis and ventricular phenotype diagnosed by workflow including endomyocardial biopsy (EMB) guided by 3D electroanatomic mapping (3D-EAM). METHODS: We prospectively enrolled patients with suspected myocarditis and VAs, undergoing cardiac magnetic resonance imaging, coronary angiography, 3D-EAM, and EMB guided by 3D-EAM. At follow-up, sustained VAs were detected by device interrogation and 24-hour electrocardiographic Holter monitoring. RESULTS: We enrolled 54 consecutive patients (mean age 41 ± 14 years; 32(59%) men) with normal ventricular function; left ventricular and right ventricular (RV) late gadolinium enhancement was present, respectively, in 21 (46%) and 6 (13%) of the 46 patients who underwent cardiac magnetic resonance. In 31 patients, the histological diagnosis was myocarditis, while in 14 patients, focal replacement myocardial fibrosis (FRMF); in 9 patients, specimens were inadequate (diagnostic yield of EMB 83%). 3D-EAM showed a larger endocardial scar area for both ventricles in myocarditis than in FRMF (RV bipolar mean scar area 22 ± 16 cm2 vs 3 ± 2 cm2; P = .02; left ventricular bipolar mean scar area 13 ± 5 cm2 vs 4 ± 2 cm2; P = .02, respectively). At a follow-up of 21 months, freedom from sustained VAs was 58% in myocarditis and 92% in FRMF (log-rank, P = .008). Histological diagnosis of myocarditis and RV endocardial scar were independent predictors of sustained VAs (P = .02 for both). CONCLUSION: Our data highlight the need for 3D-EAM-guided EMB in apparently healthy young patients with suspected myocarditis and VAs.

Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction.

PURPOSE: To test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). METHODS: We selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. RESULTS: Overall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (-20.1 ± 3.1% vs -21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (-19.7 ± 2.9% vs -21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was -21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was -16.4%. CONCLUSIONS: At CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.

Impact of baseline calibration on semiquantitative assessment of myocardial perfusion reserve by adenosine stress MRI.

In this study, we sought to investigate the impact of baseline calibration, which is used in quantitative cardiac MRI perfusion analysis to correct for surface coil inhomogeneity and noise, on myocardial perfusion reserve index (MPRI) and its contribution to previously reported paradoxical low MPRI < 1.0 in patients with unobstructed coronary arteries. Semiquantitative perfusion analysis was performed in 20 patients with unobstructed coronary arteries undergoing stress/rest perfusion CMR and in ten patients undergoing paired rest perfusion CMR. The following baseline calibration settings were compared: (1) baseline division, (2) baseline subtraction and (3) no baseline calibration. In uncalibrated analysis, we observed ~ 20% segmental dispersion of signal intensity (SI)-over-time curves. Both baseline subtraction and baseline division reduced relative dispersion of t0-SI (p < 0.001), but only baseline division corrected for dispersion of peak-SI and maximum upslope also (p < 0.001). In the assessment of perfusion indices, however, baseline division resulted in paradoxical low MPRI (1.01 ± 0.23 vs. 1.63 ± 0.38, p < 0.001) and rest perfusion index (RPI 0.54 ± 0.07 vs. 0.94 ± 0.12, p < 0.001), respectively. This was due to a reversed ratio of blood-pool and myocardial baseline-SI before the second perfusion study caused by circulating contrast agent from the first injection. In conclusion, baseline division reliably corrects for inhomogeneity of the surface coil sensitivity profile facilitating comparisons of regional myocardial perfusion during hyperemia or at rest. However, in the assessment of MPRI, baseline division can lead to paradoxical low results (even MPRI < 1.0 in patients with unobstructed coronary arteries) potentially mimicking severely impaired perfusion reserve. Thus, in the assessment of MPRI we propose to waive baseline calibration.

The assessment of treatment outcomes in patients with acute viral myocarditis by speckle tracking and tissue Doppler methods.

OBJECTIVES: The aim was to evaluate the role of tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), to identify myocardial dysfunction, and to evaluate myocardial segmental deformation in acute viral myocarditis. METHODS: Twenty-one patients and twelve healthy children were studied prospectively. The TDI and STE were performed before and after treatment. The myocardial velocities (Sm , Em , and Am ) and time intervals (isovolumic contraction, isovolumic relaxation, and ejection times [ET]) at interventricular septum (IVS), left, and right ventricular basal segments were examined by TDI. The left ventricular global longitudinal strain (LVGLS) and strain rate (LVGLSR), left ventricular global circumferential strain (LVGCS) and strain rate (LVGCSR), and right ventricular global longitudinal strain (RVGLS) and strain rate (RVGLSR) were examined by STE. RESULTS: Sm and Em at IVS and at LV, ET at IVS, ET at RV, ET at LV were significantly lower in patients before treatment than controls. LVGLS, LVGLSR, LVGCS, LVGCSR, RVGLS, RVGLSR were significantly decreased in patients before treatment than controls. There was significant improvement for LVGLS, LVGLSR, LVGCS, LVGCSR, and RVGLS in patients after treatment. Sm , Em , and Am at LV were significantly lower in patients before treatment than in patients after treatment. In spite of improvements, Sm , Em , and ET at IVS, LVGLS, LVGLSR, LVGCS, LVGCSR were significantly lower in patients after treatment than controls. CONCLUSIONS: The TDI and STE were useful methods for detection of early myocardial dysfunction and evaluation of treatment outcomes in acute viral myocarditis.

Incremental value of extracellular volume assessment by cardiovascular magnetic resonance imaging in risk stratifying patients with suspected myocarditis.

Cardiovascular magnetic resonance imaging (CMR) has become a key investigative tool in patients with suspected myocarditis. However, the prognostic implications of T1 mapping, including extracellular volume (ECV) calculation, is less clear. Patients with suspected myocarditis who underwent CMR evaluation, including T1 mapping at our institution were included. CMR findings including late gadolinium enhancement (LGE), left ventricular ejection fraction (LVEF), native T1 mapping, and ECV calculation were associated with first major adverse cardiac events (MACE). MACE included a composite of all-cause death, heart failure hospitalization, heart transplantation, documented sustained ventricular arrhythmia, and recurrent myocarditis. One hundred seventy-nine patients with a mean age of 49 ± 15 years were identified. Seventy nine individuals (44%) were female. Mean LVEF was 48 ± 16. At a median follow-up of 4.1 [interquartile-range (IQR) 2.2-6.1] years, 22 (12%) patients experienced a MACE. Mean ECV (per 10%) was significantly associated with MACE (HR 2.09, 95% CI 1.07-4.08, p = 0.031). Presence of ECV ≥ 35% demonstrated significant univariable association with MACE (HR 3.3, 95% CI 1.43-7.97, p = 0.005) and such association was maintained when adjusted to LVEF (HR 3.42, 95% CI 1.42-7.94, p = 0.006). ECV ≥ 35% portended a greater than threefold increased hazards to MACE adjusted to LGE presence (HR 3.14, 95% CI 1.29-7.36, p = 0.012). In patients without LGE, ECV ≥ 35% portended a greater than sixfold increased hazards (HR 6.6, p = 0.010). In the multivariable model including age, LVEF and LGE size, only ECV ≥ 35% maintained its significant association with outcome. ECV calculation by CMR is a useful tool in the risk stratification of patients with clinically suspected myocarditis, incremental to LGE and LVEF.

Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

BACKGROUND: To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). METHODS: A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. RESULTS: In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P < .001). There were no significant differences among LLC, T2-weighted short inversion time inversion recovery (STIR) sequences, early (EGE), and late (LGE) gadolinium-enhancement sequences for diagnosis of AM. The AUC for qualitative (T2-weighted STIR 0.92, EGE 0.87 and LGE 0.88) and quantitative (ER 0.89 and global RE 0.80) analyses were also similar. CONCLUSIONS: Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models.

The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l-1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency echocardiography allows reliable in vivo cardiac assessment in adult zebrafish and make recommendations for optimizing data acquisition and analysis. This enabling technology reveals new insights into zebrafish cardiac physiology and provides an imaging platform for zebrafish-based translational research.

Noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse.

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.

Sex and gender differences in myocarditis and dilated cardiomyopathy.

Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is, in turn, a major cause of acute DCM in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery, and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy.

Clinical applications of cardiac magnetic resonance imaging.

As a direct result of the rapid technical progress which has been realized regarding hardware and software, cardiovascular magnetic resonance imaging (CMR) is increasingly established as an important method in the diagnosis of cardiovascular disease. Numerous clinical and experimental studies have demonstrated the equality or even superiority of CMR compared to other imaging modalities such as nuclear medicine or transthoracic echocardiography. Particular strengths of CMR are the ability to overcome anatomical limitations (such as poor acoustic window), a multimodality approach to comprehensively answer various aspects of cardiac disease, and the absence of ionizing radiation during the exam. Main clinical applications of CMR include assessment of ventricular function, myocardial viability, myocardial perfusion, valvular disease, differential diagnosis of inflammatory heart disease and cardiomyopathies, congenital heart disease and structural abnormalities. In the assessment of coronary artery disease (CAD) by CMR, analysis of global and regional myocardial function is enhanced by examination of myocardial viability and perfusion. This non-invasive diagnostic ''triad'' confers CMR a unique methodological strength for a comprehensive evaluation of CAD within one single exam session. In particular, late gadolinium enhancement scar imaging by CMR is currently the most accurate non-invasive method to examine myocardial viability. In several studies on the prognostic value of CMR in CAD assessment, normal adenosine-stress CMR was highly predictive for a good prognosis, thus able to identify patients in whom invasive coronary angiography can be deferred safely. Regarding myocarditis, CMR is evolving as the most accurate imaging technique. Challenges for future development of the role of CMR in clinical routine will most likely not only include technical improvement, but also a larger CMR scanner availability, optimized cost-efficiency, increased awareness and competence to be achieved by an extended education and training in CMR.

Assessment of myocardial recovery in a patient with acute myocarditis supported with a left ventricular assist device: a case report.

Acute myocarditis may present with profound hemodynamic compromise; however, spontaneous resolution of the inflammatory process may occur in up to half of such patients. In patients with fulminant myocarditis, mechanical circulatory support may serve as a bridge to myocardial recovery. In this report we describe a 35-year-old man with acute myocarditis who required left ventricular assist device support as a bridge to recovery, and suggest a method for determining the suitability and timing of device explantation. A combination of echocardiography, right heart catheterization, exercise testing and serial endomyocardial biopsies was used to determine the resolution of myocarditis, recovery of myocardial function and timing for device explantation. Successful device explantation was performed after 37 days of device support. Further study is required to assess the role of ventricular assist devices in combination with immunosuppressive therapy in the management of fulminant myocarditis.

Acute rheumatic fever in an Arabian Gulf country--effect of climate, advantageous socioeconomic conditions, and access to medical care.

An eleven-year study of the incidence and consequences of acute rheumatic fever was carried out in a country in which a uniform climate together with national characteristics of insularity, wealth, and unrestricted access to free medical care contribute prominently to the epidemiologic milieu. Study subjects were 86 children, aged four to fourteen years, satisfying criteria for acute rheumatic fever. Study methods included clinical evaluation, standard laboratory studies, and echocardiography. A declining incidence of rheumatic episodes, ranging from 1.06 to 18.6/100,000 population (average 11.2/100,000), was identified. The course of the episode was generally mild. Arthritic findings predominated (92%), followed by carditis identified clinically in 43% and, with the addition of echocardiography, in 71%. Residual valvular regurgitation, as a longer term consequence, persisted in 46% of those with auscultatory confirmation of valvulitis. No recurrences were identified. Comparison with countries of similar socioeconomic status revealed relatively unimportant differences. Comparison with nearby disadvantaged countries identified striking contrast. It may be concluded that among the contributing factors, for the improvement in the incidence and sequelae of a rheumatic episode, are an advantaged socioeconomic environment and accessibility to unlimited medical care.

Echocardiographic assessment of left ventricular wall motion in myocarditis.

Segmental wall motion abnormalities are common in patients with myocarditis. Left ventricular (LV) regional wall motion was assessed in six patients with myocarditis by two-dimensional echocardiography. Some of our patients demonstrated regional thinning of the wall, similar to myocardial infarction. Therefore, segmental wall motion abnormalities with or without regional wall thinning detected by two-dimensional echocardiography cannot be used to differentiate myocarditis from coronary artery disease. Nevertheless, echocardiography can be performed repeatedly and is useful for evaluating the severity of myocarditis by assessing LV regional wall motion abnormalities, changes in LV wall thickness and cardiac pump function during the course of the disease.