Carlos L. Alviar

Antihypertensive Efficacy of Hydrochlorothiazide as Evaluated by Ambulatory Blood Pressure Monitoring : A Meta-Analysis of Randomized Trials

OBJECTIVES The purpose of this study was to evaluate the antihypertensive efficacy of hydrochlorothiazide (HCTZ) by ambulatory blood pressure (BP) monitoring. BACKGROUND HCTZ is the most commonly prescribed antihypertensive drug worldwide. More than 97% of all HCTZ prescriptions are for 12.5 to 25 mg per day. The antihypertensive efficacy of HCTZ by ambulatory BP monitoring is less well defined. METHODS A systematic review was made using Medline, Cochrane, and Embase for all the randomized trials that assessed 24-h BP with HCTZ in comparison with other antihypertensive drugs. RESULTS Fourteen studies of HCTZ dose 12.5 to 25 mg with 1,234 patients and 5 studies of HCTZ dose 50 mg with 229 patients fulfilled the inclusion criteria. The decrease in 24-h BP with HCTZ dose 12.5 to 25 mg was systolic 6.5 mm Hg (95% confidence interval: 5.3 to 7.7 mm Hg) and diastolic 4.5 mm Hg (95% confidence interval: 3.1 to 6.0 mm Hg) and was inferior compared with the 24-h BP reduction of angiotensin-converting enzyme inhibitors (mean BP reduction 12.9/7.7 mm Hg; p < 0.003), angiotensin-receptor blockers (mean BP reduction 13.3/7.8 mm Hg; p < 0.001), beta-blockers (mean BP reduction 11.2/8.5 mm Hg; p < 0.00001), and calcium antagonists (mean BP reduction 11.0/8.1 mm Hg; p < 0.05). There was no significant difference in both systolic (p = 0.30) and diastolic (p = 0.15) 24-h BP reduction between HCTZ 12.5 mg (5.7/3.3 mm Hg) and HCTZ 25 mg (7.6/5.4 mm Hg). However, with HCTZ 50 mg, the reduction in 24-h BP was significantly higher (12.0/5.4 mm Hg) and was comparable to that of other agents. CONCLUSIONS The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes. Because outcome data at this dose are lacking, HCTZ is an inappropriate first-line drug for the treatment of hypertension.

Treatment of Obstructive Hypertrophic Cardiomyopathy Symptoms and Gradient Resistant to First-Line Therapy With β-Blockade or Verapamil

Background—There is controversy about preferred methods to relieve obstruction in hypertrophic cardiomyopathy patients still symptomatic after &bgr;-blockade or verapamil. Methods and Results—Of 737 patients prospectively registered at our institution, 299 (41%) required further therapy for obstruction for limiting symptoms, rest gradient 61±45, provoked gradient 115±49 mm Hg, and followed up for 4.8 years. Disopyramide was added in 221 (74%) patients and pharmacological control of symptoms was achieved in 141 (64%) patients. Overall, 138 (46%) patients had surgical relief of obstruction (91% myectomy) and 6 (2%) alcohol septal ablation. At follow-up, resting gradients in the 299 patients had decreased from 61±44 to 10±25 mm Hg (P<0.0001); New York Heart Association class decreased from 2.7±0.7 to 1.8±0.5 (P<0.0001). Kaplan–Meier survival at 10 years in the 299 advanced-care patients was 88% and did not differ from nonobstructed patients (P=0.28). Only 1 patient had sudden death, a low annual rate of 0.06%/y. Kaplan–Meier survival at 10 years in the advanced-care patients did not differ from that expected in a matched cohort of the US population (P=0.90). Conclusions—Patients with obstruction and symptoms resistant to initial pharmacological therapy with &bgr;-blockade or verapamil may realize meaningful symptom relief and low mortality through stepped management, adding disopyramide in appropriately selected patients, and when needed, by surgical myectomy.

Correlation of Angiographic Late Loss With Neointimal Proliferation in Stents Evaluated by OCT and Histology in Porcine Coronary Arteries

OBJECTIVES We aimed to evaluate the correlation of angiographic late loss (LL) with the degree of in-stent neointimal proliferation assessed by optical coherence tomography (OCT) and histology. BACKGROUND Angiographic LL is the most common endpoint used in clinical trials for the evaluation of the efficacy of drug-eluting stents (DES). However, there are few data in regards to the accuracy of angiographic LL in the evaluation of DES displaying lower degrees of neointimal proliferation. METHODS A total of 49 stents (36 DES and 13 bare-metal stents) were deployed in coronary arteries of 23 domestic swine and followed up for 28 or 90 days, thus obtaining different degrees of neointimal proliferation. Each stent was divided into 8 to 9 segments along the longitudinal axis to match corresponding histological cross sections. Angiographic LL was calculated at each segment throughout the entire length of the stent and compared with in-stent neointimal thickness (NT) obtained by OCT and histology. RESULTS A total of 382 angiographic segments were suitable for matched comparison with both OCT and histological findings. The mean LL at follow-up was 0.60 ± 0.57 mm (range: -0.46 to 2.3 mm) for all segments. Approximately 13.9% of stent segments had a LL between -0.5 and 0 mm, and 22.5% had a LL greater than 1.0 mm. The correlation between OCT and histology for the evaluation of NT was adequate regardless the level of angiographic LL. In addition, overall correlations between angiographic LL and NT by OCT or histology were adequate (R = 0.77 and 0.63, respectively). However, angiographic LL showed a poor correlation with NT by OCT or histology at a value <0.55 mm (R = 0.38 and 0.15, respectively). CONCLUSIONS Angiographic LL below a threshold value of 0.55 mm correlates poorly with NT obtained by OCT and histology. These results suggest a cautious interpretation is needed to evaluate angiographic endpoints in DES trials in which LL values below this threshold are reported.

'Chasing the dragon': new knowledge for an old practice.

Heroin administration by “chasing the dragon,” whereby the user places freebase heroin on aluminum foil, heats it below with a flame, and inhales the pyrolysate through a straw, can be associated with the rare development of a delayed-onset spongiform leukoencephalopathy. We report the case of a 46-year-old woman with a psychiatric diagnosis of depression and heroin dependence by “chasing the dragon” admitted with features of altered mental status and later development of catatonia, abulia, and akinetic mutism. A brain magnetic resonance image evidenced bilateral symmetric high-signal lesions in the white matter of the cerebrum and cerebellum on T2-weighted images compatible with toxic leukoencephalopathy. The patients condition resolved after a hospital stay of 2 months with supportive treatment. Acute onset of neurobehavioral changes, including confusion, apathy, and cerebellar signs in a person with exposure to heroin, should prompt one to consider toxic leukoencephalopathy as a cause of presentation.

Impact of adventitial neovascularisation on atherosclerotic plaque composition and vascular remodelling in a porcine model of coronary atherosclerosis

AIMS There is little in vivo data in regards to the impact of adventitial neovascularisation on vascular remodelling and plaque composition. Using a porcine model of coronary atherosclerosis, we aimed to determine the impact of adventitial neovascularisation on plaque composition and vascular remodelling evaluated by IVUS. METHODS AND RESULTS Coronary atherosclerosis was induced by adventitial delivery of lipids and a high cholesterol diet. At termination all vessels were analysed using IVUS to determine the degree of remodelling of each individual segment containing atherosclerotic lesions. Then, each segment was correlated with its correspondent histological frame for plaque composition and neovessel density. A total of 57 atherosclerotic lesions at different stages of development were analysed. The total neovessel count (TNC) correlated to the degree of plaque burden (15.6+/-7.2 TNC in 60% stenosis, p<0.01) and to the amount of intra-plaque collagen (32.4+/-14.1%, lower TNC tertile versus 47.5+/-8.9% upper TNC tertile, p< 0.01). The amount of intra-plaque SMC content inversely correlated with the TNC (49.7+/-18.9% versus 36.4+/-14.4%, lower versus upper tertiles, p<0.05). Plaques with the highest TNC showed higher remodelling indexes by IVUS (0.89+/-0.32 in lower TNC tertile versus 1.36+/-0.73 in upper TNC tertile, p<0.05) and higher macrophage cell content (161.42+/-157.6 in lower TNC tertile versus 340.6+/-127.2 in upper TNC tertile, p<0.05) compared to non-remodelled segments. CONCLUSIONS Adventitial neovascularisation is more prominent in positively remodelled segments and appears to be associated to SMC loss, increase collagen deposition and localised macrophage infiltration.

Efficacy and safety of dual calcium channel blockade for the treatment of hypertension: a meta-analysis.

BACKGROUND Dual calcium-channel blocker (CCB) with a dihydropyridine (DHP) and a nondihydropyridine (NDHP) has been proposed for hypertension treatment. However, the safety and efficacy of this approach is not well known. METHODS A MEDLINE/EMBASE/CENTRAL search for randomized clinical trials published on this topic from 1966 to February 2012 was performed. Efficacy outcomes of decrease in systolic (SBP) and diastolic (DBP) blood pressures from baseline, changes in heart rate (HR), and adverse effects were compared between dual CCB therapy vs. DHP or NDHP. SBP, DBP, and HR were expressed as weighted mean deviation (WMD). RESULTS A total of 6 studies with 153 patients were included. Dual CCB produced a significantly greater reduction in SBP (21.6±9.2 mmHg) from baseline than DHP (10.3±6.3 mmHg (WMD = 10.9 mmHg, P < 0.0001)) or NDHP (8.9±4.2 mmHg (WMD = 14.1 mmHg, P = 0.002)). Dual CCB therapy reduced DBP from baseline more than either monotherapy (dual CCB = 17.5±10.2 mmHg vs. DHP = 11.6±8.7 mmHg, WMD = 5.5 mmHg, P < 0.001; and NDHP = 10.5±5.6 mmHg, WMD = 5.3 mmHg, P = 0.03). Dual CCB therapy had significantly lower HR compared to DHP (P < 0.001) but was comparable to NDHP (P = 0.12) (Delta change dual CCB = -4.0±3.5 vs. DHP = -2.0±1.5 and NDHP = -6.0±5.0 beats/min). Dual CCB therapy did not increase adverse effects. CONCLUSIONS Dual CCB therapy lowers blood pressure significantly better than CCB monotherapy, without an increase in adverse events. However, given the lack of long-term outcome data on efficacy and safety, dual CCB therapy should be used with restraint, if at all. Large-scale long-term trials are needed to further evaluate such a strategy.

Infectious atherosclerosis: Is the hypothesis still alive? A clinically based approach to the dilemma

Among the multiple factors involved in the pathophysiology of heart disease, infections have been proposed to play a role in atherosclerosis with most of the available evidence implicating Chlamydia pneumonia, influenza virus and Mycoplasma pneumoniae. Based on a model case presentation, we speculate that in the absence of traditional risk factors and in the context of an ongoing respiratory infection caused by a pro-inflammatory pathogen (M. pneumoniae) along with a past positive serologic history for potentially proven atherogenic microorganism (C. pneumoniae) and infection may elicit potentially pathogenic events on vascular wall cells and leukocytes of atheromatous lesions, supporting the hypothesis that such infections may potentiate atherosclerotic cardiovascular disease (CVD).

Bilateral Bochdalek Hernias Presenting as Respiratory Failure in an Elderly Patient

Bochdalek hernia occurs from a congenital defect of the diaphragm, allowing the passage of abdominal structures into the thoracic cavity, limiting lung expansion and ventilatory function. Bochdalek hernia is common in neonates but rarely occur in adults; there are only 4 documented cases in the elderly population. We present a case of an 88-year-old woman with severe hypoxia and respiratory failure that required ventilatory support, in whom bilateral Bochdalek hernias progressed over the years and severely invaded the thoracic cavity, causing acute decompensation. This is a rare condition in adults but can cause substantial morbidity when the involvement of the thoracic cavity is severe.

ASSOCIATION OF MARITAL STATUS WITH VASCULAR DISEASE IN DIFFERENT ARTERIAL TERRITORIES: A POPULATION BASED STUDY OF OVER 3.5 MILLION SUBJECTS

The association of marital status and cardiovascular disease (CVD) is limited to small studies comparing married to non-married subjects. We sought to investigate the odds of CVD in married, single, divorced and widowed subjects in a large prospective cohort. Over 3.5 million participants were

Mild hyperkalemia and low eGFR a tedious recipe for cardiac disaster in the elderly: an unusual reversible cause of syncope and heart block

Hyperkalemia affects the myocardial tissue producing electrocardiographic abnormalities, such as prolongation of the P-R interval, tall peaked T waves, a reduction in the amplitude and an increase in the duration of P wave, and atrial and ventricular arrhythmias, including variable degree heart blocks. Elderly patients are particularly predisposed to developing hyperkalemia and the associated abnormalities due to an age-related reduction in glomerular filtration rate and pre-existing medical problems. Therefore, the impact of aging on potassium homeostasis must be taken into consideration, and preventive measures, such as early recognition of possible hyperkalemia in the geriatric population treated with certain medications or supplements must be investigated. The threshold for cardiac arrhythmias in the elderly can be lower than the general population. We report 3 unusual cases of mild hyperkalemia in elderly patients presenting with hypotension, syncope and variable degree heart blocks which resolved spontaneously with the correction of hyperkalemia.