Reduced Cardiac Index Reserve and Hypovolemia in Severe Falciparum Malaria.

BACKGROUND: Impaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance. METHODS: Patients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography. RESULTS: Patients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale. CONCLUSIONS: Patients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve.

Cell-Free Hemoglobin Is Associated With Increased Vascular Resistance and Reduced Peripheral Perfusion in Severe Malaria.

BACKGROUND: In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria. METHODS: Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The systemic vascular resistance index (SVRI) was estimated from the echocardiographic cardiac index and the mean arterial pressure. RESULTS: SVRI and hematocrit levels were lower and plasma CFH and asymmetric dimethylarginine levels were higher in patients with malaria, compared with healthy participants. In multivariate linear regression models for mean arterial pressure or SVRI in patients with severe malaria, hematocrit and CFH but not asymmetric dimethylarginine were significant predictors. The SVRI was lower in patients with suspected bacterial sepsis than in those with severe malaria, after adjustment for hematocrit and age. Plasma CFH levels correlated positively with the core-peripheral temperature gradient and plasma lactate levels and inversely with the perfusion index. Impaired peripheral perfusion, as reflected by a low perfusion index or a high core-peripheral temperature gradient, predicted mortality in patients with severe malaria. CONCLUSIONS: CFH is associated with mean arterial pressure, SVRI, and peripheral perfusion in patients with severe malaria. This may be mediated through the nitric oxide scavenging potency of CFH, increasing basal vascular tone and impairing tissue perfusion.

Modes of death and clinical outcomes in adult patients with hypertrophic cardiomyopathy in Thailand.

BACKGROUND: There are limited data about modes of death and major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM) in South East Asian population. The aim of the study was to examine modes of death and clinical outcomes in Thai patients with HCM. METHODS: Between January 1, 2009 and December 31, 2013, 166 consecutive patients with HCM diagnosed in our institution were evaluated. Five patients were excluded because of non-Thai ethnic groups (n = 3) and diagnosis of myocardial infarction at initial presentation documented by coronary angiography (n = 2). The final study population consisted of 161 patients with HCM. HCM-related deaths included: (1) sudden cardiac death (SCD) - death due to sudden cardiac arrest or unexpected sudden death; (2) heart failure - death due to refractory heart failure; or (3) stroke - death due to embolic stroke associated with atrial fibrillation. MACEs included: (1) SCD, sudden unexpected aborted cardiac arrest, fatal, or nonfatal ventricular arrhythmia (ventricular fibrillation or sustained ventricular tachycardia); (2) heart failure (fatal or non-fatal), or heart transplantation; or (3) stroke - fatal or non-fatal embolic stroke associated with atrial fibrillation. RESULTS: One hundred and sixty-one Thai patients with HCM (age 66 ± 16 years, 58% female) were enrolled. Forty-two patients (26%) died over a median follow-up period of 6.8 years including 25 patients (16%) with HCM-related deaths (2%/year). The HCM-related deaths included: heart failure (52% of HCM-related deaths; n = 13), SCD (44% of HCM-related deaths; n = 11), and stroke (4% of HCM-related deaths, n = 1). The SCDs occurred in 6.8% of patients (1%/year). Eighty-four major MACEs occurred in 65 patients (41, 5%/year). The MACEs included: 40 heart failures in which 2 patients underwent heart transplants; 22 SCDs and nonfatal ventricular arrhythmias; and 22 fatal or nonfatal strokes. CONCLUSIONS: The most common mode of death in adult patients with HCM in Thailand was heart failure followed by SCD. About one-third of the patients experiencing heart failure died during the 6.8 years of follow-up. SCDs occurred in 7% of patients (1%/year), predominantly in the fourth decade or later.

Clinical Results of Left Atrial Appendage Closure with Watchman Device in Patients with Atrial Fibrillation.

BACKGROUND: In patient with non-valvular atrial fibrillation (AF), over 90% of thrombus accumulation originates in the left atrial appendage (LAA). Warfarin significantly reduces risk of stroke. However, long-term anticoagulant therapy is associated with a significant risk of major bleeding, particularly in elderly. Transcatheter occlusion of left atrial appendage with Watchman device has proved to be non-inferior to warfarin in preventing stroke in non-valvular AF patients. No previous report of transcatheter occlusion of LAA was found in Thailand OBJECTIVE: To evaluate short-term results of left atrial appendage closure with the Watchman® device in patient with non-valvular AF performed at King Chulalongkorn Memorial Hospital (KCMH). MATERIAL AND METHOD: Between November 2012 and December 2014, 12 consecutives patients underwent percutaneous transcatheter left atrial appendage closure. Data included patient's characteristics, embolic risk factors, bleeding risk score, procedural finding, complications, in-hospital outcomes, and antithrombotic management were retrospectively reviewed RESULTS: Percutaneous LAA occlusion was successfully performed in all 12 patients. The mean age was 71.2 ± 8.1 years. The history of previous bleeding was seen in four patients (33%). All patients had good left ventricular systolic function. The mean CHADS2 score was 3.2 ± 1.3, the mean CHA2DS2-VASc score was 4.8 ± 1.6 and the mean HAS-BLED score was 2.5 ± 0.9. The average LAA orifice diameter was 21.7 ± 3.4 mm, and the median implant size was 27.0 mm. The compression ratio was 15.2 ± 6.2%. Three patients (25%) were performed under general anesthesia, nine patients (75%) were performed with local anesthesia. The averageprocedure time was 61.2 ± 18.5 minutes. The average fluoroscopy time was 6.8 ± 3.3 minutes. There was no device embolization or pericardial effusion. There was no periprocedural cerebral event, assess site bleeding, or death during hospital admission. Mild peridevice leak was observed in three patients (25%), and all had disappeared on TEE performed at the 45-day follow-up. The median length of stay was two days. CONCLUSION: The result of the present study showed that percutaneous LAA occlusion with the Watchman device was feasible and safe. The successfulness of the procedures and periprocedural complications were similar to standard in literature.

Double orifice mitral valve: a report of two cases with different severity and treatment.

Background: Double orifice mitral valve (DOMV), a rare congenital heart disease, is characterized by a 2-orifice mitral valve (MV) separated by a tissue bridge, causing a spectacles-like morphology. DOMV can present with various severity ranging from asymptomatic to severe valvular dysfunction including mitral regurgitation (MR) and mitral stenosis (MS), as well as symptoms from coexisting congenital anomalies. Echocardiography is the mainstay of the investigation for a DOMV. We described two cases with DOMV who presented with different disease severity resulting in different treatment decisions. Case Description: In the first case, a 52-year-old woman presented with overt left-sided heart failure. The echocardiogram revealed DOMV with ruptured chordae tendineae of the anterior mitral valve leaflet (AMVL) causing severe MR which led the patient to undergo surgical MV replacement. Intraoperative findings confirmed a diagnosis of DOMV. After surgery, the patient could perform daily activities and light exercises without recurrent heart failure. In the second case, on the other hand, a 36-year-old woman was incidentally diagnosed with DOMV from an echocardiographic workup for symptomatic premature ventricular contraction (PVC). After controlled PVC with radiofrequency ablation, her symptom completely resolved and DOMV was classified as asymptomatic which led to the decision of a watchful waiting strategy. Conclusions: These cases highlight the diversity of DOMV manifestations and the importance of appropriate investigations, particularly echocardiography, to evaluate valvular pathology and contemplating the treatment strategy.

Idiopathic pericardial effusion in patients with hypertrophic cardiomyopathy.

The aims of this study were to examine the prevalence of moderate to large (moderate-large) idiopathic pericardial effusion (i-PEF) in patients with hypertrophic cardiomyopathy (HCM) and to identify clinical and echocardiographic hemodynamic profiles associated with pericardial effusion. A total of 292 adult patients with HCM were studied. Fifteen patients with a history of factors associated with pericardial effusion including myocardial infarction, heart surgery or cardiac procedure within the last 12 months, autoimmune disease, hydralazine use, chronic kidney disease stage 3-4, tuberculosis, and malignancy were excluded. Of 277 eligible patients with HCM, 11 patients (4%) with moderate-large i-PEF were identified. Clinical tamponade was present in 1 patient. Compared to patients with HCM who had no or small pericardial effusion, patients with moderate-large i-PEF were younger and more likely to have right ventricular (RV) hypertrophy and reverse septal curvature. These patients also exhibited a greater maximal septal thickness, mean and systolic pulmonary pressure, and right atrial pressure (p < 0.05 for all). Pericardial fluid analysis and histopathological exams were performed in 7 and 3 patients, respectively. All examinations revealed transudative and nonspecific etiology of pericardial effusion. Idiopathic pericardial effusion and cardiac tamponade in patients with HCM was uncommon. The pathophysiology involved in pericardial effusion remains undetermined. Patients with moderate-large i-PEF frequently exhibited a phenotype of pulmonary hypertension and RV pressure overload.

Higher prevalence of QTc interval prolongation among virologically suppressed older people with HIV.

OBJECTIVE: To assess the prevalence, and factors associated with QTc interval prolongation, among 383 virologically suppressed people with HIV (PWH), without evidence of cardiovascular disease and active opportunistic infections in Thailand. DESIGN: Cross-sectional study. METHODS: Resting 12-lead digital ECGs were performed in 2019. QT interval corrected for heart rate (QTc) >450 ms in males and >460 ms in females was defined as QTc interval prolongation. We used multivariable logistic regression to investigate factors associated with QTc interval prolongation. RESULTS: Mean (standard deviation) age was 56 (5.5) years and 42% were female. The median current CD4+ was 619 (interquartile range [IQR] 487, 769) cells/mm 3 . The median duration of antiretroviral therapy (ART) was 11.9 (IQR 7.1-16.1) years. Commonly used ART were rilpivirine (37.9%), efavirenz (20.1%), atazanavir/ritonavir (15.7%), lopinavir/ritonavir (12.3%) and dolutegravir (5%). The prevalence of QTc interval prolongation was 22.7%. In multivariable analysis, older age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12, P  = 0.005), female sex (OR 1.69, 95% CI 1.01-2.82, P  = 0.046) and increasing BMI (OR 1.08, 95% CI 1.01-1.15, P  = 0.03) were associated with QTc interval prolongation. With every 1-year increase in age, the odds of QTc interval prolongation increased by 7%. CONCLUSIONS: In this well-suppressed aging Asian HIV cohort, the prevalence of QTc interval prolongation was relatively high, and associated with increasing age, female sex, and higher BMI. For PLWH with these characteristics, QTc interval should be monitored before and after initiating any medications known to prolong QTc intervals, to prevent fatal cardiac arrhythmias.

Home Blood Pressure Control and Drug Prescription Patterns among Thai Hypertensives: A 1-Year Analysis of Telehealth Assisted Instrument in Home Blood Pressure Monitoring Nationwide Pilot Project.

BACKGROUND: Several interventions have been proposed to improve hypertension control with various outcomes. The home blood pressure (HBP) measurement is widely accepted for assessing the response to medications. However, the enhancement of blood pressure (BP) control with HBP telemonitoring technology has yet to be studied in Thailand. OBJECTIVE: To evaluate the attainment of HBP control and drug prescription patterns in Thai hypertensives at one year after initiating the TeleHealth Assisted Instrument in Home Blood Pressure Monitoring (THAI HBPM) nationwide pilot project. METHODS: A multicenter, prospective study enrolled treated hypertensive adults without prior regular HBPM to obtain monthly self-measured HBP using the same validated, oscillometric telemonitoring devices. The HBP reading was transferred to the clinic via a cloud-based system, so the physicians can adjust the medications at each follow-up visit on a real-life basis. Controlled HBP is defined as having HBP data at one year of follow-up within the defined target range (<135/85 mmHg). RESULTS: A total of 1,177 patients (mean age 58 ± 12.3 years, 59.4% women, 13.1% with diabetes) from 46 hospitals (81.5% primary care centers) were enrolled in the study. The mean clinic BP was 143.9 ± 18.1/84.3 ± 11.9 mmHg while the mean HBP was 134.4 ± 15.3/80.1 ± 9.4 mmHg with 609 (51.8%) patients having HBP reading <135/85 mmHg at enrollment. At one year of follow-up after implementing the HBP telemonitoring, 671 patients (57.0%) achieved HBP control. Patients with uncontrolled HBP had a higher prevalence of dyslipidemia and greater waist circumference than the controlled group. The majority of uncontrolled patients were still prescribed only one (36.0%) or two drugs (34.4%) at the end of the study. The antihypertensive drugs were not uptitrated in 136 (24%) patients with uncontrolled HBP at baseline. Calcium channel blocker was the most prescribed drug class (63.0%) followed by angiotensin-converting enzyme inhibitor (44.8%) while the thiazide-type diuretic was used in 18.9% of patients with controlled HBP and 16.4% in uncontrolled patients. CONCLUSION: With the implementation of HBP telemonitoring, the BP control rate based on HBP analysis was still low. This is possibly attributed to the therapeutic inertia of healthcare physicians. Calcium channel blocker was the most frequently used agent while the diuretic was underutilized. The long-term clinical benefit of overcoming therapeutic inertia alongside HBP telemonitoring needs to be validated in a future study.

Hypertension Subtypes among Thai Hypertensives: An Analysis of Telehealth-Assisted Instrument in Home Blood Pressure Monitoring Nationwide Pilot Project.

BACKGROUND: White-coat hypertension (HT), masked HT, HT with white-coat effect, and masked uncontrolled HT are well-recognized problems of over- and undertreatment of high blood pressure in real-life practice. However, little is known about the true prevalence in Thailand. OBJECTIVES: To examine the prevalence and characteristics of each HT subtype defined by mean home blood pressure (HBP) and clinic blood pressure (CBP) using telemonitoring technology in Thai hypertensives. METHODS: A multicenter, observational study included adult hypertensives who had been diagnosed for at least 3 months based on CBP without the adoption of HBP monitoring. All patients were instructed to manually measure their HBP twice a day for the duration of at least one week using the same validated automated, oscillometric telemonitoring devices (Uright model TD-3128, TaiDoc Corporation, Taiwan). The HBP, CBP, and baseline demographic data were recorded on the web-based system. HT subtypes were classified according to the treatment status, CBP (≥or <140/90 mmHg), and mean HBP (≥or <135/85 mmHg) into the following eight subtypes: in nonmedicated hypertensives, there are four subtypes that are normotension, white-coat HT, masked HT, and sustained HT; in treated hypertensives, there are four subtypes that are well-controlled HT, HT with white-coat effect, masked uncontrolled HT, and sustained HT. RESULTS: Of the 1,184 patients (mean age 58 ± 12.7 years, 59% women) from 46 hospitals, 1,040 (87.8%) were taking antihypertensive agents. The majority of them were enrolled from primary care hospitals (81%). In the nonmedicated group, the prevalence of white-coat and masked HT was 25.7% and 7.0%, respectively. Among the treated patients, the HT with white-coat effect was found in 23.3% while 46.7% had uncontrolled HBP (a combination of the masked uncontrolled HT (9.6%) and sustained HT (37.1%)). In the medicated older subgroup (n = 487), uncontrolled HBP was more prevalent in male than in female (53.6% vs. 42.4%, p=0.013). CONCLUSIONS: This is the first nationwide study in Thailand to examine the prevalence of HT subtypes. Almost one-fourth had white-coat HT or HT with white-coat effect. Approximately half of the treated patients especially in the older males had uncontrolled HBP requiring more intensive interventions. These results emphasize the role of HBP monitoring for appropriate HT diagnosis and management. The cost-effectiveness of utilizing THAI HBPM in routine practice needs to be examined in the future study.

Vascular and hemostatic alterations associated with pulmonary hypertension in ß-thalassemia hemoglobin E patients receiving regular transfusion and iron chelation.

INTRODUCTION: Pulmonary hypertension (PH) is the commonest cardiac complication in ß-thalassemia intermedia, including ß-thalassemia/hemoglobin E (ß-thal/HbE), and is strongly associated with splenectomy. We aimed to define the prevalence and comprehensively explore mechanisms of PH in ß-thal/HbE patients receiving regular transfusion and iron chelation, which were reported to alleviate PH. MATERIALS AND METHODS: ß-Thal/HbE patients receiving regular transfusion and iron chelation over one year were enrolled. Patients at risk for PH were defined by tricuspid-regurgitant-jet-velocity (TRV) ≥ 2.5 m/s. Laboratory and echocardiographic variables were compared with healthy controls. RESULTS: There were 68 ß-thal/HbE, including 31 (45.6%) splenectomized patients, and 38 controls included for analysis. PH was detected in 29 ß-thal/HbE (42.6%). ß-Thal/HbE with PH had a significant reduction in nitric oxide metabolites (NOx) but elevations in thrombin-antithrombin (TAT) complex, soluble thrombomodulin (sTM), endothelin-1 (ET-1) and flow-mediated dilation (FMD) values compared to those without PH (all, p < 0.05). TRV was significantly correlated with NOx, TAT, sTM, ET-1 and FMD values (r = -0.514, r = 0.281, r = 0.313, r = 0.245 and r = -0.474; all p < 0.05). Erythropoietic activity, serum ferritin, circulating total tissue factor (TF) antigen, microparticle-associated TF activity, microparticle's procoagulant activity and soluble p-selectin levels were not different between PH and non-PH subgroups. Notably, there were no significant associations between splenectomy and PH. CONCLUSIONS: PH remains prevalent in ß-thal/HbE patients receiving long-term transfusion and iron chelation. PH is not associated with splenectomy status but correlated with NO depletion, TF-independent hypercoagulability and endothelial perturbation.

Depleted nitric oxide and prostaglandin E2 levels are correlated with endothelial dysfunction in ß-thalassemia/HbE patients.

Mechanisms of vascular disorders in ß-thalassemia/HbE patients remain poorly understood. In the present study, we aimed to determine the presence of endothelial dysfunction and its association with altered vascular mediators in this population. Forty-three ß-thalassemia/HbE patients without clinically documented vascular symptoms and 43 age-sex-matched healthy controls were enrolled. Endothelial function was assessed using flow-mediated dilatation (FMD) before and after administration of nitroglycerine (NTG). ß-Thalassemia/HbE patients showed a significant endothelial dysfunction using FMD. The percentage change in the brachial artery diameter before NTG was significantly lower in the thalassemia group compared to the control (5.0 ± 5.9 vs. 9.0 ± 4.0%, p < 0.01) while no significant differences after NTG (18.4 ± 8.3 vs. 17.8 ± 6.3%, p = 0.71). Plasma nitric oxide metabolites (NO x ) and prostaglandin E2 (PGE2) levels were significantly decreased in ß-thalassemia/HbE (117.2 ± 27.3 vs. 135.8 ± 11.3 µmol/L, p < 0.01) and (701.9 ± 676.0 vs. 1374.7 ± 716.5 pg/mL, p < 0.01), respectively, while a significant elevation in soluble thrombomodulin levels in ß-thalassemia/HbE (3587.7 ± 1310.0 vs. 3093.9 ± 583.8 pg/mL, p = 0.028). NO x and PGE2 levels were significantly correlated with FMD (r = 0.27, p = 0.025) and (r = 0.35, p = 0.003), respectively. These findings suggest roles for endothelial mediators and a new mechanism underlying endothelial dysfunction in ß-thalassemia/HbE patients.