Higher incidence of vasodilator-induced left ventricular cavity dilation by PET when compared to treadmill exercise-ECHO in hypertrophic cardiomyopathy.

BACKGROUND: Vasodilator-induced transient left ventricular cavity dilation (LVCD) by positron emission tomography (PET) is associated with microvascular dysfunction in hypertrophic cardiomyopathy (HCM). Here we assessed whether HCM patients who develop LVCD by PET during vasodilator stress also develop LV cavity dilation by echocardiography (ECHO-LVCD) following exercise stress. METHODS: A retrospective analysis of cardiac function and myocardial blood flow (MBF) was conducted in 108 HCM patients who underwent perfusion-PET and exercise-ECHO as part of their clinical evaluation. We performed a head-to-head comparison of LV volumes and ejection fraction (LVEF) at rest and stress (during vasodilator stress, post-exercise), in 108 HCM patients. A ratio > 1.13 of stress to rest LV volumes was used to define PET-LVCD, and a ratio > 1.17 of stress to rest LVESV was used to define ECHO-LVCD. Patients were divided into 2 groups based on the presence/absence of PET-LVCD. MBF and myocardial flow reserve were quantified by PET, and global longitudinal strain (GLS) was assessed by ECHO at rest/stress in the two groups. RESULTS: PET-LVCD was observed in 51% (n = 55) of HCM patients, but only one patient had evidence of ECHO-LVCD (ratio = 1.36)-this patient also had evidence of PET-LVCD (ratio = 1.20). The PET-LVCD group had lower PET-LVEF during vasodilator stress, but ECHO-LVEF increased in both groups post-exercise. The PET-LVCD group demonstrated higher LV mass, worse GLS at rest/stress, and lower myocardial flow reserve. Incidence of ischemic ST-T changes was higher in the PET-LVCD group during vasodilator stress (42 vs 17%), but similar (30%) in the two groups during exercise. CONCLUSION: PET-LVCD reflects greater degree of myopathy and microvascular dysfunction in HCM. Differences in the cardiac effects of exercise and vasodilators and timing of stress-image acquisition could underlie discordance in ischemic EKG changes and LVCD by ECHO and PET, in HCM.

Angiotensin Receptor-Neprilysin Inhibitors and the Natriuretic Peptide Axis.

PURPOSE OF THE REVIEW: The purpose of this review is to describe the effects of angiotensin receptor neprilysin inhibitor (ARNI) therapy on the natriuretic peptide axis (NPA), with a particular focus on B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP), and C-type natriuretic peptide (CNP) to better understand the biology behind the improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). RECENT FINDINGS: BNP, ANP, and CNP are the three main natriuretic peptides (NP); they share a common structure and ultimately mediate their actions by activating cyclic guanosine monophosphate (cGMP). ARNI therapy results in a decrease of N-terminal pro-BNP (NT-proBNP) and increase of BNP levels respectively. It is been questioned whether these changes may result from unique laboratory assays characteristics rather than actual biological implications. It appears to be that the prognostic accuracy of BNP for cardiovascular outcomes remains independent and comparable to that of NT-proBNP while on ARNI therapy. ANP levels also increase with ARNI therapy, but no consistent change has been described for CNP levels. There is evidence that the changes in BNP and NT-proBNP correlate with improvement in echocardiographic parameters of volume and function. The dual effect of neprilysin inhibition and angiotensin receptor blockade has substantial implications on the natriuretic peptide axis (NPA). The changes seen in BNP and NT-proBNP specifically have shown to correlate with improvement in echocardiographic parameters. Further results exploring the biologic effects of ARNI therapy on other NPs are still pending and likely will provide further insights in the mechanisms behind the improvement in cardiac function and clinical outcomes.

Lp(a): Addressing a Target for Cardiovascular Disease Prevention.

PURPOSE OF REVIEW: To review the current recommendations for lipoprotein(a) (Lp(a)) screening, the evidence behind the thresholds for increased cardiovascular disease (CVD) risk, and the available data supporting Lp(a) lowering. RECENT FINDINGS: Lp(a) is almost entirely genetically determined and has an independent causal association with CVD. Measurement of Lp(a) is challenging given the structural heterogeneity of apolipoprotein a (apo(a)), for which isoform-insensitive immunoassays should be used. Current guidelines do not recommend treatment to lower Lp(a) but rather focus on intensified preventive measures including low-density lipoprotein cholesterol (LDL-C) lowering in patients with high Lp(a). Evidence suggests that levels higher than 50 mg/dL (125 nmol/L) identify significantly increased CVD risk. Mendelian randomization studies suggest that in order to have a clinically significant reduction in coronary heart disease, Lp(a) levels should be reduced by at least 60-70 mg/dL to attain a significant benefit. Ongoing studies of targeted therapy with antisense oligonucleotides (ASO) have shown promising reductions in Lp(a) up to 80%, but a cardiovascular outcomes trial is needed. There is unquestionably an increased risk for CVD in patients with elevated Lp(a); however, measurement assay issues and the lack of Lp(a)-targeted therapies with proven outcome reduction limit the clinical utility of this important risk factor. Available evidence suggesting specific thresholds for clinically significant CVD risk are based on European or Caucasian populations, not accounting for important racial differences. Novel Lp(a)-targeted emerging therapies may need to account for an expected reduction of at least 60-70 mg/dL to achieve a clinically significant benefit.

Pre-Heart Failure Longitudinal Change in a Hispanic/Latino Population-Based Study: Insights From the Echocardiographic Study of Latinos.

BACKGROUND: Pre-heart failure (pre-HF) is an entity known to progress to symptomatic heart failure (HF). OBJECTIVES: This study aimed to characterize pre-HF prevalence and incidence among Hispanics/Latinos. METHODS: The Echo-SOL (Echocardiographic Study of Latinos) assessed cardiac parameters on 1,643 Hispanics/Latinos at baseline and 4.3 years later. Prevalent pre-HF was defined as the presence of any abnormal cardiac parameter (left ventricular [LV] ejection fraction <50%; absolute global longitudinal strain <15%; grade 1 or more diastolic dysfunction; LV mass index >115 g/m2 for men, >95 g/m2 for women; or relative wall thickness >0.42). Incident pre-HF was defined among those without pre-HF at baseline. Sampling weights and survey statistics were used. RESULTS: Among this study population (mean age: 56.4 years; 56% female), HF risk factors, including prevalence of hypertension and diabetes, worsened during follow-up. Significant worsening of all cardiac parameters (except LV ejection fraction) was evidenced from baseline to follow-up (all P < 0.01). Overall, the prevalence of pre-HF was 66.7% at baseline and the incidence of pre-HF during follow-up was 66.3%. Prevalent and incident pre-HF were seen more with increasing baseline HF risk factor burden as well as with older age. In addition, increasing the number of HF risk factors increased the risk of prevalence of pre-HF and incidence of pre-HF (adjusted OR: 1.36 [95% CI: 1.16-1.58], and adjusted OR: 1.29 [95% CI: 1.00-1.68], respectively). Prevalent pre-HF was associated with incident clinical HF (HR: 10.9 [95% CI: 2.1-56.3]). CONCLUSIONS: Hispanics/Latinos exhibited significant worsening of pre-HF characteristics over time. Prevalence and incidence of pre-HF are high and are associated with increasing HF risk factor burden and with incidence of cardiac events.

Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination. OBJECTIVES: This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk. METHODS: Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models. RESULTS: Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS. CONCLUSIONS: Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions.

A case of chemotherapy-induced coronary vasospasm in a patient with colorectal cancer.

Colorectal cancer kills nearly 700,000 people each year worldwide. The use of chemotherapeutic agents in the treatment of colorectal cancer has broadened considerably over the past few decades. The cardiovascular care of patients being treated with these agents has received increasing attention over recent years due to the known cardiovascular toxicities associated with certain treatment regimens, but there may still be unidentified cardiovascular toxicities. Here we present a case of a patient with colorectal cancer without any modifiable cardiovascular risk factors who experienced coronary vasospasm shortly after initiation of therapy with 5-flourouracil, leucovorin, and oxaliplatin with bevacizumab, despite having previously tolerated boluses of 5-flourouracil alone without incident. Coronary vasospasm attributed to this combination of chemotherapy has never before been reported. Additionally, our case and other available literature demonstrate the efficacy of dihydropyridine calcium channel blocker therapy in treatment of vasospasm induced by chemotherapeutic agents. .

Low Left Atrial Strain Is Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy Patients.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) and left atrial (LA) structural remodeling are common in hypertrophic cardiomyopathy (HCM) patients, who are also at risk for adverse cardiovascular outcomes. OBJECTIVE: We assessed whether PAF and/or LA remodeling was associated with adverse outcomes in HCM. METHODS: We retrospectively studied 45 HCM patients with PAF (PAF group) and 59 HCM patients without atrial fibrillation (AF; no-AF group). LA/left ventricular (LV) function and mechanics were assessed by echocardiography. Patients were followed for development of the composite endpoint comprising heart failure, stroke, and death. RESULTS: Clinical/demographic characteristics, degree of LV hypertrophy, and E/e' were similar in the two groups The PAF group had significantly higher LA volume, but lower LA ejection fraction (LAEF), LA contractile, and reservoir strain/strain rate than the no-AF group. During follow-up, 27 patients developed the composite endpoint. Incidence of the composite endpoint was similar in the two groups. Absolute values of 23.8% for reservoir strain and 10.2% for conduit strain were the best cutoffs for the composite endpoint, using receiver operating characteristic analysis. Kaplan-Meier survival analysis showed lower event-free survival in patients with reservoir strain ≤23.8% or conduit strain ≤10.2%. Univariate Cox analysis revealed an association between female sex, LAEF, LA reservoir/conduit strain, and LV global longitudinal strain with the composite endpoint. The association between LA reservoir/conduit strain and the composite endpoint persisted after controlling for age, sex, LAEF, and LV global longitudinal strain. CONCLUSIONS: In this pilot HCM patient study, PAF was associated with a greater degree of LA myopathy, and low LA reservoir and conduit strain were associated with higher risk for adverse cardiovascular outcomes.

Hypertrophic Cardiomyopathy Patients With Paroxysmal Atrial Fibrillation Have a High Burden of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging.

OBJECTIVES: This study hypothesized that paroxysmal atrial fibrillation (PAF) reflects the presence of a more severe cardiac hypertrophic cardiomyopathy (HCM) phenotype. BACKGROUND: HCM is characterized by myocyte hypertrophy, fibrosis, and a high prevalence of PAF. It is currently unresolved whether atrial fibrillation (AF) is a marker or a mediator of adverse outcomes in HCM. METHODS: This study retrospectively examined 45 HCM patients who underwent cardiovascular magnetic resonance (CMR) imaging in sinus rhythm. The function of all 4 cardiac chambers was assessed, as well as late gadolinium enhancement (LGE) in the left atrium (LA) and left ventricle (LV), as indicators of fibrosis. A fat-saturated, 3-dimensional inversion recovery-prepared, fast-spoiled, gradient-recalled echo sequence, and the image intensity ratio method were used to measure LA-LGE; LGE in the LV was quantified using a semi-automated threshold technique. RESULTS: HCM patients (n = 45) were divided into 2 groups (PAF, no AF) based on history of PAF. All HCM patients had LGE in the LA posterior wall. The PAF group (n = 18) had higher LA volume, a lower LA ejection fraction, a lower global peak longitudinal LA strain (PLAS), and a higher amount of LA-LGE compared with the no AF group (n = 27). A modest inverse association was noted between the LA ejection fraction, PLAS, and LA-LGE; a positive association was present between LV-LGE and LA-LGE. The PAF group had lower ejection fractions in the LV, right atrium, and right ventricle compared with those in the no AF group. CONCLUSIONS: PAF is associated with a greater degree of structural LA remodeling and global myopathy, which suggests a more severe cardiac HCM phenotype.

Regulatory T-Cell Dynamics in Cutaneous and Mucocutaneous Leishmaniasis due to Leishmania braziliensis.

To evaluate the dynamics of regulatory T cells (Tregs) during tegumentary leishmaniasis, we assessed peripheral blood and biopsies from 54 patients. Patients with cutaneous leishmaniasis (CL) had a decreased proportion of Tregs in the peripheral blood, but the proportion was higher in the biopsies of lesions. During treatment of CL, circulating Tregs increased reaching normal proportions, whereas antigen-specific interferon-γ responses diminished. By contrast, circulating Tregs from mucosal leishmaniasis patients failed to normalize during treatment. C-C chemokine receptor type 5 was expressed on a large proportion of Tregs at the site of infection. These results demonstrate increased Tregs at the site of infection, possibly homing from the peripheral circulation.

Percepción sobre el profesionalismo médico en estudiantes del último año de medicina en una universidad peruana / Perception of medical professionalism in students of the last year of their career in a Peruvian university

RESUMEN Objetivo: Describir conceptos, experiencias y perspectivas que alumnos del último año de medicina en una universidad peruana tienen respecto al Profesionalismo Médico. Material y Métodos : Se aplicó una encuesta a alumnos que cursaban la rotación clínica final de su último (7º) año de estudios en la Facultad de Medicina de la Universidad Peruana Cayetano Heredia, durante el año 2015. Resultados : El porcentaje de respuestas fue 90,5%. Las tres respuestas más comunes fueron ética (51,2%), buena comunicación médico-paciente (43%) y conocimientos (41,9%). El 81,4 % de los estudiantes estuvo "de acuerdo" o "muy de acuerdo" con el hecho de que profesionalismo puede ser aprendido y enseñado. El contacto con modelos positivos del personal docente de la Facultad (4,26/5,00) fue considerado el método más útil para el aprendizaje sobre profesionalismo médico, en tanto que sólo el 25,6% consideró adecuado el número de actividades dedicadas a la enseñanza del tema. Conclusiones: Los Internos de medicina consideran a la ética, una buena relación médico-paciente, conocimiento, respeto y responsabilidad como principales atributos del profesionalismo médico. Percibieron que su concepto de profesionalismo fue más influenciado por modelos positivos que por actividades académicas formales.

SUMMARY Objective : To describe concepts, experiences, and perspectives from senior (7th Year) medical students of a Peruvian university, regarding Medical Professionalism. Material and Methods : A survey was applied to medical students that completed their Internship at the Faculty of Medicine of the Universidad Peruana Cayetano Heredia, during 2015. Results : The percentage of responses reached a 90.5%. The three most common responses were ethics (51.2%), a good doctor-patient relationship (43%), and knowledge (41.9%). Approximately eighty-one percent (81.4%) of the students "agreed" or "strongly agreed" with the fact that professionalism can be learned and taught. The contact with positive models from the faculty (4.26 / 5.00) was considered as the most useful method for learning about professionalism, while only 25.6% considered adequate the number of activities dedicated to the teaching of the topic. Conclusions: Medical interns consider ethics, good patient-physician communication, knowledge, respect and responsibility as the main attributes of medical professionalism. They perceived that their concept of professionalism was more influenced by positive faculty models than by formal academic activities.

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy.

Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using 13NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E', late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation+ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation+ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation+ vs 1.09 ± 0.39, LV cavity dilation-; p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.