Write a Scientific Paper (WASP): Past and anticipated trends in cardiology service requirements at Mater Dei Hospital, Malta.

INTRODUCTION: The requirement for medical services fluctuates. This study was carried out in order to attempt to extrapolate the service requirements for various cardiology services at Mater Dei Hospital, Malta over the coming five years, based on service demands from previous years. METHODS: Past annual data was obtained from hospital records for various services (to 2017). Linear regression was carried out using a bespoke Excel™ spreadsheet in order to extrapolate possible services requirements up to 2022. RESULTS: All services are expected to increase, with forecasts ranging between 41 and 354%, depending on services being considered. DISCUSSION: It is easy to "get on with it" and perform the work required at the workplace but this study has shown that it is equally important to anticipate demands lest lack of planning leads to long and important waiting lists for critical diagnostics and treatments. Health care provision requirements are increasing worldwide. Even using conservative estimates and in the absence of the creation of new services, the demands for extant services are likely to continue to grow. Unless medium term plans are made for hardware, software, physical space and staffing, and the funding thereof, waiting lists for investigations in this speciality are bound to rise. This may be mitigated by novel treatments but since these cannot be predicted, it would be safer and wiser to plan ahead lest we are overwhelmed. This paper has also shown how WASP (Write a Scientific Paper) precepts can be applied to elegantly study a problem and write up a paper.

The incidence, predictors, and prognosis of acute kidney injury after transcatheter aortic valve implantation
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INTRODUCTION AND AIMS: Transcatheter aortic valve implantation (TAVI) is an alternative procedure for patients with symptomatic aortic stenosis unfit for open heart surgery. Notwithstanding the safer profile, TAVI can still result in serious complications including acute kidney injury (AKI). MATERIALS AND METHODS: We conducted a single-center retrospective study to investigate the incidence of AKI following TAVI, identify any predictors, and assess the impact on patient survival. RESULTS: A total of 104 patients underwent TAVI at a mean age of 76.7 ± 7.2 years. AKI occurred in 35.9% of patients; 26.2% stage 1, 5.8% stage 2, and 3.9% stage 3. These patients had higher incidence of chronic kidney disease (CKD) (37.8 vs. 18.2%; p = 0.035), higher median EuroSCORE-II (4.2, IQR: 5.7 vs. 2.7, IQR: 3.6; p = 0.019), longer hospital stay (6 days, IQR: 7 vs. 5 days, IQR: 3; p = 0.016), and higher all-cause mortality (35.1 vs. 12.1%, p = 0.01) compared to patients without AKI. None of the patient mortality was directly related to the TAVI-AKI event. EuroSCORE-II (OR: 1.19, CI: 1.05 - 1.37, p = 0.009) and CKD (OR: 2.74, CI: 1.10 - 6.82, p = 0.03) were established as independent predictors for AKI. Cumulative survival was lower in patients with AKI (log-rank; χ2 = 6.43, p = 0.011). AKI was established as a hazard for mortality (HR: 2.97, CI: 1.23 - 7.19, p = 0.016). CONCLUSION: More than a third of patients undergoing TAVI developed AKI. These had significantly higher incidence of CKD, higher EuroSCORE-II, higher all-cause mortality, and longer hospital stay. Finally, EuroSCORE-II and CKD were established as independent predictors for AKI and can therefore be used for risk stratification.
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Co-registration of angiography and intravascular ultrasound images through image-based device tracking.

OBJECTIVES: To determine the feasibility of automated co-registration of angiography and intravascular ultrasound (IVUS) to facilitate integration of these two imaging modalities in a synchronous manner. BACKGROUND: IVUS provides cross-sectional imaging of coronary arteries but lacks overview of the vascular territory provided by angiography. Co-registration of angiography and IVUS would increase utility of IVUS in the clinical setting. METHODS: Forty-nine consecutive patients undergoing surveillance for cardiac allograft vasculopathy with angiography and IVUS of the left anterior descending artery (LAD) were enrolled. A pre-IVUS angiogram of the LAD was performed followed by an ECG-triggered fluoroscopy (ECGTF) during IVUS pullback at 0.5 mm/s using an automatic pullback device. ECGTF was used to track the IVUS catheter during pullback and establish a spatial relationship to the pre-IVUS angiogram. Angio-IVUS co-registration was performed with a research prototype (Siemens Healthcare, Germany) and accuracy was evaluated by distance mismatch between angiography and IVUS images at vessel bifurcations. RESULTS: Median age was 54 (44.5, 67) years. The population was 82.6% male with minimal risk factors. The median (IQR) co-registration distance mismatch measured at 108 bifurcations in 42 (85%) patients was 0.35 (0.00-1.16) mm. Seven patients were excluded due to inappropriate data acquisition (n = 3) and failure of tracking (n = 4), e.g., due to overlapping sternal wires. Estimated effective radiation dose for ECGTF was 0.09 mSv. CONCLUSION: This study demonstrates the feasibility of angio-IVUS co-registration which may be used as a clinical tool for localizing IVUS cross-sections along an angiographic roadmap. © 2015 Wiley Periodicals, Inc.

Extracorporeal shockwave myocardial therapy is efficacious in improving symptoms in patients with refractory angina pectoris--a multicenter study.

OBJECTIVE: Medically refractory angina remains a significant health concern despite major advances in revascularization techniques and emerging medical therapies. We aimed to determine the safety and efficacy of extracorporeal shockwave myocardial therapy (ESMT) in managing angina pectoris. METHODS: A single-arm multicenter prospective study was designed aiming to determine the safety and efficacy of ESMT. Patients of functional Canadian Cardiovascular Society class II-IV, despite stable and optimal medical management, with documented myocardial segments with reversible ischemia and/or hibernation on the basis of echocardiography/single-photon emission computerized tomography (SPECT) were enrolled from 2010 to 2012. A total of 111 patients were enrolled, 33 from Indonesia, 21 from Malaysia, and 57 from Philippines. Patients underwent nine cycles of ESMT over 9 weeks. Patients were followed up for 3-6 months after ESMT treatment. During follow-up, patients were subjected to clinical evaluation, the Seattle Angina Questionnaire, assessment of nitrate intake, the 6-min walk test, echocardiography, and SPECT. RESULTS: The mean age of the population was 62.9±10.9 years. The summed difference score on pharmacologically induced stress SPECT improved from 9.53±17.87 at baseline to 7.77±11.83 at follow-up (P=0.0086). Improvement in the total Seattle Angina Questionnaire score was seen in 83% of patients (P<0.0001). Sublingual nitroglycerin use significantly decreased (1.14±1.01 tablets per week at baseline to 0.52±0.68 tablets per week at follow-up; P=0.0215). There were no changes in left ventricular function on echocardiography (0.33±9.97, P=0.93). The Canadian Cardiovascular Society score improved in 74.1% of patients. CONCLUSION: This multicenter prospective trial demonstrated that ESMT is both a safe and an efficacious means of managing medically refractory angina.

Evaluation of coronary adventitial vasa vasorum using 3D optical coherence tomography--animal and human studies.

OBJECTIVES: This study sought to evaluate adventitial vasa vasorum (VV) in vivo with novel imaging technique of optical coherence tomography (OCT). METHODS: To verify OCT methods for quantification of VV, we first studied 2 swine carotid arteries in a model of focal angiogenesis by autologous blood injection, and compared microchannel volume (MCV) by OCT and VV by m-CT, and counts of those. In OCT images, adventitial MC was identified as signal-voiding areas which were located within 1 mm from the lumen-intima border. After manually tracing microchannel areas and the boundaries of lumen-intima and media-adventitial in all slices, we reconstructed 3D images. Moreover, we performed with OCT imaging in 8 recipients referred for evaluation of cardiac allograft vasculopathy at 1 year after heart transplantation. MCV and plaque volume (PV) were assessed with 3D images in each 10-mm-segment. RESULTS: In the animal study, among the 16 corresponding 1-mm-segments, there were significant correlations of count and volume between both the modalities (count r(2) = 0.80, P < 0.01; volume r(2) = 0.50, P < 0.01) and a good agreement with a systemic bias toward underestimation with m-CT. In the human study, there was a significant positive correlation between MCV and PV (segment number = 24, r(2) = 0.63, P < 0.01). CONCLUSION: Our results suggest that evaluation of MCV with 3D OCT imaging might be a novel method to estimate the amount of adventitial VV in vivo, and further has the potential to provide a pathophysiological insight into a role of the VV in allograft vasculopathy.

Safety and efficacy of extracorporeal shock wave myocardial revascularization therapy for refractory angina pectoris.

OBJECTIVE: To assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris. PATIENTS AND METHODS: A single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires. RESULTS: Fifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10). CONCLUSION: In this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.

Fractional flow reserve with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic myocardial bridging.

BACKGROUND: Myocardial bridging (MB) results in compression of the coronary artery lumen in systole, extending into diastole with resultant hemodynamic alternation as reflected by fractional flow reserve (FFR). MB has also been associated with coronary endothelial dysfunction. The objective of this study was to investigate relationship between FFR with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic MB. METHODS AND RESULTS: Seventeen consecutive patients who had cardiac catheterization assessment of MB were enrolled. The patients were divided into 2 groups according to normal (% increase in coronary blood flow [%CBF] ≥50%, n=7) or impaired (%CBF <50%, n=10) coronary microvascular endothelial function assessed on vasoreactivity in the coronary artery with intracoronary infusion of acetylcholine (Ach). Myocardial ischemia was then assessed using FFR at rest and during i.v. dobutamine infusion challenge across the MB with intracoronary pressure wires. FFR was significantly decreased at peak dobutamine infusion compared to at rest in the impaired group (0.85±0.06 vs. 0.91±0.05, P=0.001), but not in the normal group (0.93±0.05 vs. 0.91±0.07, P=0.618). Both FFR at rest and at peak dobutamine infusion had a positive correlation with %CBF by Ach in the impaired group (r(2)=0.46, P=0.030; r(2)=0.52, P=0.018, respectively). CONCLUSIONS: Microvascular endothelial dysfunction was associated with decreased FFR at peak dobutamine stress in patients with symptomatic MB.

Coronary endothelial function in patients with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) has been associated with increased risk for cardiovascular events, possibly mediated by endothelial dysfunction. The current study evaluates the association between invasive coronary endothelial dysfunction and OSA in patients with nonobstructive coronary atherosclerosis. METHODS: All patients who had undergone both polysomnography and an invasive coronary vasomotor study at the Mayo Clinic, Rochester, Minnesota, from January 1997 to August 2011 were identified (n=143). OSA was defined as an apnea-hypopnea index of 5 or higher. Three endpoints of coronary endothelial function - percentage change in coronary artery diameter at the mid and distal left anterior descending artery to intracoronary acetylcholine and percentage change in coronary blood flow to intracoronary acetylcholine - were assessed. Differences between patients with OSA (n=102) and those without OSA (n=41) were evaluated using multivariate analysis of variance. Follow-up mortality data were collected and Kaplan-Meier curves were plotted to evaluate differences in mortality between patients with and without OSA. RESULTS: Patients with OSA were more likely to have hypertension compared with patients without OSA. OSA was not significantly associated with coronary endothelial dysfunction on univariate analysis (P=0.23) and after adjustment for hypertension (P=0.19). Similarly, there was no significant difference in coronary endothelial function in patients who had oxygen desaturation of less than 90% during polysomnography (P=0.42). There was a trend toward higher mortality in patients with OSA compared with those without OSA, but this did not reach statistical significance (5 vs. 0% at 10 years, P=0.25). CONCLUSION: The current study suggests that OSA is not an independent risk factor for coronary endothelial dysfunction in patients with early coronary atherosclerosis. Adverse coronary outcomes in patients with OSA may be independent of coronary endothelial dysfunction.

Pneumatic compression for embolic protection during upper extremity endovascular intervention.

Embolic protection devices are occasionally employed during endovascular interventions to prevent complications caused by embolic debris. However, these devices have imperfect efficacy, confer risk of endovascular trauma, and are expensive. We report a patient with giant cell arteritis and symptomatic axillary artery stenosis, with a perceived elevated risk of distal embolization during endovascular intervention. We describe a straightforward embolic protection technique of brachial pressure cuff inflation during endovascular intervention and aspiration of displaced thrombotic material from the static column of blood. This novel, effective, and cost-free technique could also be employed in other vascular beds during endovascular intervention.

Sex-related differences in fractional flow reserve-guided treatment.

BACKGROUND: Sex-specific differences affect the evaluation, treatment, and prognosis of coronary artery disease. We tested the hypothesis that long-term outcomes of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) are different between women and men. METHODS AND RESULTS: Consecutive 1090 patients, referred for PCI and undergoing FFR measurements at the Mayo Clinic between October 2002 and December 2009, were included in this registry study. Clinical events were compared between the sexes during a median follow-up of 50.9 months. Of all patients, women had higher FFR adjusted by visual coronary stenosis than men (P=0.03). The Kaplan-Meier percent of major adverse cardiac events at 5 years was 35% in women and 38% in men (P=0.54). Interestingly, in patients undergoing PCI with an FFR <0.75, the incidence of death or myocardial infarction was significantly higher in women than in men (hazard ratio, 2.16; 95% confidence interval, 1.04-4.51; P=0.04). Moreover, compared with patients with FFR >0.80, deferral of PCI for those with FFR between 0.75 and 0.80 was associated with an increased rate of major adverse cardiac events, particularly death or myocardial infarction in women (hazard ratio, 3.25; 95% confidence interval, 1.56-6.74; P=0.002) and revascularization in men (hazard ratio, 2.66; 95% confidence interval, 1.66-4.54; P<0.001). CONCLUSIONS: Long-term outcome differs between women and men undergoing FFR-guided PCI. Our data suggest that the sex-based treatment strategy is necessary to further optimize prognosis of patients with coronary artery disease.

Emergency cardiac support with extracorporeal membrane oxygenation for cardiac arrest.

A 46-year-old woman with no major medical history presented to the emergency department with chest pain and evidence of anterior, anterolateral, and inferior ST-elevation myocardial infarction. Her condition quickly deteriorated into cardiogenic shock with ventricular arrhythmia. Despite revascularization of the left anterior descending artery and intravenous inotrope and antiarrhythmic therapy, her unstable hemodynamics and arrhythmias persisted. Early emergency initiation of venoarterial extracorporeal membrane oxygenation (ECMO) led to prompt hemodynamic and rhythm stability; however, adequate endogenous cardiac output did not ensue, and she was not able to be weaned from ECMO until hospital day 8. She subsequently recovered and continues to do well in the outpatient setting. This case demonstrates the remarkable hemodynamic and rhythm stability that early initiation of ECMO can provide in the setting of unstable myocardial infarction.

Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation.

BACKGROUND: The aim of the study was to assess temporal changes in plaque size and components after heart transplantation (HTx), and to evaluate the differences in treatment effects on plaque progression between sirolimus and calcineurin inhibitors (CNIs). METHODS: The study comprised 146 HTx recipients who were converted from CNIs to sirolimus as primary immunosuppressant (sirolimus group, n = 61) and those who were maintained on CNIs (CNI group, n = 85). A retrospective compositional analysis of serial virtual histology-intravascular ultrasound was performed. RESULTS: During a median follow-up of 2.8 years, there was a significant difference in plaque volume in favor of sirolimus between groups (p = 0.004). When subjects were sub-classified according to the time interval between HTx and study inclusion, those in the early group (≤2 years after HTx) had a greater increase in plaque volume (p = 0.006), characterized by a higher progression rate of fibrous plaque volume (p = 0.01). The treatment difference between groups in plaque volume was identified in the early group in favor of sirolimus with attenuating effects on the progression of fibrous plaque component (both p = 0.03 for interaction). By contrast, there were significant differences in necrotic core and dense calcium volume (both p < 0.05 for interaction) in favor of CNIs in the late group (≥6 years after HTx). CONCLUSIONS: Compared with continued CNI therapy, sirolimus attenuated plaque progression in recipients with early conversion, but contributed to increases in necrotic core and dense calcium volume in those with late conversion. Our study supports the hypothesis that early initiation of sirolimus offers greater benefits in the treatment of CAV.

Repeated episodes of thrombosis as a potential mechanism of plaque progression in cardiac allograft vasculopathy.

AIMS: The pathogenesis of cardiac allograft vasculopathy (CAV) remains complex and may involve multiple mechanisms. We tested the hypothesis that the multilayer (ML) appearance, an intravascular ultrasound (IVUS) finding suggestive of repetitive thrombosis, is associated with plaque progression in heart transplant (HTx) recipients. METHODS AND RESULTS: Our study population consisted of 132 HTx recipients undergoing at least two grayscale and virtual histology (VH)-IVUS examinations. A retrospective serial analysis was performed between the first (baseline) and the last (follow-up) IVUS data during a median follow-up of 3.0 years. The subjects were divided into two groups based on the presence of the ML appearance on the baseline IVUS. At baseline, subjects with ML appearance (n = 38) had a longer time elapsed since transplant, larger vessel volume, and larger plaque volume than those without (n = 94) (all P < 0.01). Intraluminal thrombi and plaque ruptures were identified only in subjects with ML appearance (P < 0.01 vs. those without). More subjects with ML appearance at baseline developed subsequent ML formation compared with those without [21 (55%) vs. 22 (23%), P < 0.01] during follow-up. There was an increase in plaque volume, necrotic core volume, and dense calcium volume in subjects with ML appearance (all P < 0.01 vs. those without). Multivariable linear regression analysis showed that ML appearance was a potential predictor of plaque progression (regression coefficient 0.28, 95% CI 0.10-0.45, P < 0.01). CONCLUSIONS: The current study demonstrates that a finding of ML appearance, indicative of repeated episodes of mural thrombosis, is not infrequent in asymptomatic HTx recipients and possibly contributes to progression of CAV.

Coronary atherosclerosis with vulnerable plaque and complicated lesions in transplant recipients: new insight into cardiac allograft vasculopathy by optical coherence tomography.

AIMS: Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival following cardiac transplantation. Conventional imaging modalities such as angiography and intravascular ultrasound fail to characterize CAV plaque morphology. Our aim was to characterize CAV in vivo using the high spatial resolution of intracoronary optical coherence tomography (OCT). METHODS AND RESULTS: We prospectively enrolled 53 cardiac transplant patients to undergo OCT of the left anterior descending coronary artery (LAD) in addition to annual CAV screening by coronary angiography and intravascular ultrasound (IVUS). The proximal 30 mm of the LAD was divided into three segments of 10 mm each (n = 156). Segments with CAV plaque on IVUS were analysed by OCT for specific CAV morphological characteristics within the framework of three groups according to follow-up time after heart transplantation: (i) 0-3 months (n = 18), (ii) 12-36 months (n = 55), and (iii) ≥48 months (n = 83). The prevalence of atherosclerotic characteristics such as eccentric plaques, calcification, and lipid pools increased from 6, 0, and 6% in group 1 to 78, 42, and 61% in group 3, respectively (all P < 0.001). The prevalence of vulnerable plaque features such as thin-cap fibroatheroma, macrophages, and microchannels increased from 0% in group 1 to 12, 29, and 33% in group 3, respectively (P = 0.19, P = 0.006, and P = 0.003). Complicated coronary lesions such as intimal laceration, intraluminal thrombus, and layered complex plaque increased from 0% in group 1 to 18, 19, and 57% in group 3 (P = 0.009, P < 0.001, and P < 0.001). Plaque rupture was identified in 4% of group 3 segments. CONCLUSION: The current study gives new insight into CAV that extends far beyond the current concept of concentric and fibrosing vasculopathy, that is, the development of atherosclerosis with vulnerable plaque and complicated coronary lesions.

Eosinophilic endocarditis and Strongyloides stercoralis.

A 40-year-old woman from El Salvador presented with 3 months of abdominal pain and diarrhea followed by 2 weeks of atypical chest pain and exertional dyspnea and was diagnosed with eosinophilic endocarditis secondary to Strongyloides stercoralis infection. Transthoracic echocardiogram revealed apical masses in the left and right ventricles and a thickened posterior mitral valve leaflet and cardiac magnetic resonance imaging confirmed the presence of a left ventricular apical mass with diffuse subendocardial delayed enhancement consistent with endocardial fibrosis. In conclusion, eosinophilic endocarditis is a rare cause of restrictive cardiomyopathy characterized by endomyocardial fibrosis and apical thrombosis and fibrosis with frequent involvement of the posterior mitral valve leaflet.

The management of combined coronary artery disease and peripheral vascular disease.

Coronary artery disease (CAD) and peripheral vascular disease (PVD) remain highly prevalent in the population due to population ageing, smoking, diabetes, unhealthy lifestyles, and the epidemic of obesity, and frequently coexist. The management of combined CAD and PVD is a common challenge and brings with it numerous clinical dilemmas. The goal of this article is to review the prevalence of PVD and its major impact upon prognosis in patients with known CAD and in turn to review the impact of CAD upon the prognosis of patients with PVD. This review will also highlight issues related to the peri-operative evaluation and management of patients going to vascular surgery, including medical optimization as well as the performance and timing of coronary revascularization.

Lack of correlation between noninvasive stress tests and invasive coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease.

BACKGROUND: Despite a nonobstructive coronary angiogram, many patients may still have an abnormal coronary vasomotor response to provocation and to myocardial demand during stress. The ability of noninvasive stress tests to predict coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease is unknown. METHODS AND RESULTS: All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n=376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of