Frequency of Cardiac Valvulopathies in Patients With Marfan Syndrome: A Systematic Review and Meta-Analysis.

Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the I2 statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.

Non-calcified plaque in asymptomatic patients with zero coronary artery calcium score: A systematic review and meta-analysis.

BACKGROUND: There is growing interest in understanding the coronary atherosclerotic burden in asymptomatic patients with zero coronary artery calcium score (CACS). In this population, we aimed to investigate the prevalence and severity of non-calcified coronary plaques (NCP) as detected by coronary CT angiography (CCTA), and to analyze the associated clinical predictors. METHODS: This was a systematic review with meta-analysis of studies indexed in PubMed/Medline and Web of Science from inception of the database to March 31st, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I2 statistics whilst Funnel plots and Egger's test were used to assess for publication bias. RESULTS: From a total of 14 studies comprising 37808 patients, we approximated the pooled summary estimates for the overall prevalence of NCP to be 10% (95%CI: 6%-13%). Similarly, the pooled prevalence of obstructive NCP was estimated at 1.1% (95%CI: 0.7%-1.5%) from a total of 10 studies involving 21531 patients. Hypertension [OR: 1.46 (95%CI:1.31-1.62)] and diabetes mellitus [OR: 1.69 (95%CI: 1.41-1.97)] were significantly associated with developing any NCP, with male gender being the strongest predictor [OR: 3.22 (95%CI: 2.17-4.27)]. CONCLUSION: There is a low burden of NCP among asymptomatic subjects with zero CACS. In a subset of this population who have clinical predictors of NCP, the addition of CCTA has a potential to provide a better insight about occult coronary atherosclerosis, however, a risk-benefit approach must be factored in prior to CCTA use given the low prevalence of NCP.

A systematic review and meta-analysis of the prevalence, incidence, and predictors of atrial fibrillation in cardiac sarcoidosis.

BACKGROUND: The occurrence of atrial arrhythmias, in particular, atrial fibrillation (AF) in patients with cardiac sarcoidosis (CS) are of growing interest in the field of infiltrative cardiomyopathies. Via a systematic review with meta-analysis, we sought to synthesize data on the prevalence, incidence, and predictors of atrial arrhythmias as well as outcomes in patients with CS. METHODS: PubMed/Medline, Web of Science, and Scopus were systematically queried from inception until April 26th, 2023. Using the random-effects model, separate plots were generated for each effect size assessed. RESULTS: From a total of 8 studies comprising 978 patients with CS, the pooled summary estimates for the prevalence of AF was 23% (95% CI: 13%-34%). Paroxysmal AF was the most common subtype of AF (83%; 95% CI: 77%-90%), followed by persistent AF (17%; 95% CI: 10%-23%). In 9 studies involving 545 patients with CS, the pooled incidence of AF was estimated at 5%, 13.1%, and 8.9% at <2 years, 2-4 years, and > 4 years of follow-up respectively, with an overall cumulative incidence of 10.6% (95% CI: 4.9%-17.8%) over a 6-year follow-up period. Increased left atrial size and atrial 18F-fluorodeoxyglucose uptake were identified as strong independent predictors for the development of atrial arrhythmias on qualitative synthesis. CONCLUSION: The burden of AF and related arrhythmias in CS patients is considerable. This necessitates close follow-up and predictive risk-stratification tools to guide the initiation of appropriate strategies, including therapeutic interventions for prevention of AF-related embolic phenomenon, especially in those with known clinical predictors.

Near-Fatal Acute Myocardial Infarction in a Young Patient With Occlusive Coronary Artery Disease.

Acute myocardial infarction (AMI) due to obstructive coronary artery disease in young patients is an unusual event. Its clinical pattern somewhat differs from that of elderly patients, thus placing them at an increased risk of misdiagnosis, as this young population typically does not demonstrate the traditional risk factors associated with cardiovascular disease. We report the case of a 35-year-old man who presented with new-onset chest pain leading to cardiac arrest and was found to have 100% occlusion of the left anterior descending (LAD) coronary artery, which was successfully managed with the placement of a drug-eluting stent. We briefly reviewed the literature and noted that to reduce the risk of dramatic outcomes, it is imperative to include acute MI in the differential diagnosis of young patients presenting with chest pain, regardless of the presence or absence of any identifiable risk factor.

The role of ARBs alone or with HCTZ in the treatment of hypertension and prevention of cardiovascular and renal complications.

BACKGROUND: Hypertension (HTN) management guidelines stress the importance of effective blood pressure (BP) control to prevent progression to adverse cardiovascular (CV) and renal outcomes. OBJECTIVE: To review the efficacy of different angiotensin II receptor blocking agents (ARBs) as monotherapy or in combination therapy as antihypertensive agents and their effects on renal and CV outcomes beyond BP control. METHODS: The emerging use of ARBs was reviewed from the current literature (1997-2010). RESULTS: Evidence from clinical trials indicates that most patients will need > 1 agent to achieve their BP goal. First-line combination therapy is becoming increasingly accepted as standard, especially in patients with moderate to severe HTN, as combination therapy not only allows patients to benefit from additive or synergistic properties of drugs with complementary mechanisms of action, but also improves patient compliance and offers better tolerability. Furthermore, because HTN is a key risk factor for vascular disease, it is becoming clear that additional beneficial effects, such as cardio- and renoprotection, should also be considered when choosing antihypertensive agents, or combinations, for treatment. Angiotensin receptor blockers as a class of antihypertensive agents are noted for their efficacy and good tolerability in combination with other agents, especially diuretics. Irbesartan/hydrochlorothiazide (HCTZ) treatment resulted in a reduction of 27.1 and 14.6 mm Hg in systolic BP (SBP) and diastolic BP (DBP), respectively. Combination treatment of losartan, olmesartan, telmisartan, valsartan, and HCTZ all achieved significant reductions in SBP/DBP compared with monotherapy regimens. CONCLUSIONS: Early use of ARB/HCTZ combination therapy achieves critical decrease in BP and is an effective treatment for patients with moderate to severe HTN. Angiotensin receptor blockers also have renal- and CV-protective properties in conjunction with their antihypertensive effects, providing additional benefit to patients who at risk of vascular disease.

Efficacy and tolerability of nebivolol in stage I-II hypertension: a pooled analysis of data from three randomized, placebo-controlled monotherapy trials.

BACKGROUND: Nebivolol is a ß(1)-selective ß-blocker with NO-mediated vasodilatory properties, approved in the United States for the treatment of stage I-II hypertension. OBJECTIVE: The purpose of this pooled analysis was to summarize efficacy and provide a brief overview of the tolerability associated with the use of nebivolol. METHODS: PubMed was searched for randomized, double-blind, placebo-controlled, parallel-group trials of monotherapy with nebivolol for stage I-II hypertension of at least 12 weeks' duration. This article reports pooled changes in sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) at trough; proportions of responders (patients whose end-point sitting DBP at trough was <90 mm Hg or whose sitting DBP at trough had decreased from baseline by ≤10 mm Hg); and the most frequent adverse events (AEs). These data were also summarized in the subpopulation of black patients. RESULTS: The literature search yielded 3 similarly designed studies. In all 3 trials, a single-blind placebo run-in phase (4-6 weeks) was followed by randomization (baseline) and a 12-week double-blind treatment phase in which patients received nebivolol 1.25 to 30 or 40 mg/d or placebo. The primary efficacy measure in all 3 trials was the mean change from baseline in sitting DBP at 12 weeks, based on the intent-to-treat population. In the pooled sample, 930 (46.1%) patients were women, and the mean age was 53.6 years. Compared with placebo (n = 205), the reductions in DBP (up to 11.1 mm Hg), SBP (up to 12.4 mm Hg), and HR (up to 9.2 beats/min) were significantly greater with nebivolol (n = 1811) at the recommended dosages of 5-30/40 mg/d (all, P < 0.001). The most commonly reported AEs were headache (nebivolol, all dosages, 7.1%; placebo, 5.9%), fatigue (3.6% vs 1.5%, respectively), and nasopharyngitis (3.1% vs 4.4%). The efficacy and tolerability of nebivolol in black patients were similar to those observed in the total study population. CONCLUSION: Based on the pooled results from the 3 monotherapy trials reported here, nebivolol administered for 12 weeks was efficacious and generally well tolerated in patients with stage I-II hypertension.

Nebivolol efficacy and safety in patients with stage I-II hypertension.

BACKGROUND: Nebivolol is a novel, beta(1)-adrenergic receptor blocker with vasodilatory properties mediated through activation of the L-arginine/nitric oxide pathway. HYPOTHESIS: This multicenter, double-blind, parallel-group, placebo-controlled study investigated the antihypertensive efficacy and safety of nebivolol in patients with stage I through stage II hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 mm Hg and < or = 109 mm Hg). METHODS: A total of 811 patients were randomized to placebo or nebivolol 5 mg, 10 mg, or 20 mg once daily for 12 weeks. The primary efficacy endpoint was the reduction in mean trough SiDBP from baseline. RESULTS: At study end, the least squares mean reductions in trough SiDBP from baseline with nebivolol 5 mg, 10 mg, and 20 mg were - 7.8 mm Hg, - 8.5 mm Hg, and - 9.1 mm Hg, respectively, compared with - 4.6 mm Hg for placebo (P = .002 for nebivolol 5 mg, P<.001 for nebivolol 10 mg and 20 mg, vs placebo). Nebivolol treatment also produced reductions in trough sitting systolic blood pressure; however, only the 20 mg dose was statistically significant compared with placebo (-6.7 mm Hg vs - 0.4 mm Hg; P<.001). Response rates (defined as an average trough SiDBP < 90 mm Hg or a decrease by > or = 10 mm Hg from baseline at the end of the study) ranged from 66.0% to 68.9% with nebivolol 5-20 mg, compared with 49.3% with placebo (P< or =.009). Nebivolol 5 mg and 10 mg doses were well tolerated, with an overall adverse event incidence comparable to placebo. CONCLUSIONS: Once-daily nebivolol is an effective antihypertensive agent in patients with stage I-II hypertension.

Olmesartan medoxomil-based therapy for the management of hypertension.

Contemporary practice guidelines for hypertension recommend a goal systolic/diastolic blood pressure (BP) of less than 140/90 mmHg for patients with hypertension and less than 130/80 mmHg for patients with diabetes mellitus or chronic kidney disease. Current guidelines recognize that most patients will require combination therapy to achieve these BP goals and recommend that the agents used in such therapy should have complementary mechanisms of action. Olmesartan medoxomil is an angiotensin receptor blocker approved for the treatment of hypertension as monotherapy or in combination with antihypertensive agents. It is also approved in a fixed-dose combination with hydrochlorothiazide or amlodipine. Olmesartan medoxomil-based therapy can manage hypertension across a range of patient types and has demonstrated good BP-lowering efficacy and goal attainment in individuals with stage 1 or stage 2 hypertension. The comparative antihypertensive efficacy and safety of olmesartan medoxomil, as monotherapy and as part of combination therapy, has been established in several large, randomized clinical trials. This review evaluates the chemistry, efficacy and safety of olmesartan medoxomil-based therapy and its expanding role in hypertension management.

Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension.

In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlorothiazide (HCTZ), a beta-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP) and diastolic BP (DBP) to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (< 140/90 mmHg) than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/ benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients.

A review of olmesartan medoxomil monotherapy: antihypertensive efficacy similar to that of other angiotensin II receptor blocker/hydrochlorothiazide combinations?

Angiotensin II receptor blockers (ARBs) have been available in the United States since 1995. These agents have demonstrated antihypertensive efficacy at least similar to that of agents from other antihypertensive classes. Recent large-scale, randomized, controlled clinical trials have demonstrated that ARBs offer cardiovascular and renal protective benefits independent of their effects on systemic blood pressure (BP), which make them valuable as first-line antihypertensive agents, especially in high-risk patients. However, as is the case with other antihypertensive classes, monotherapy with the first-available ARBs (losartan potassium, valsartan, and irbesartan) may not provide sufficient BP reduction to achieve currently recommended BP goals in many patients. The diuretic hydrochlorothiazide is frequently added to enhance the ability of ARBs to lower BP. Several head-to-head comparison studies have shown differences in antihypertensive efficacy among the available ARBs. The newest ARB, olmesartan medoxomil, was recently compared with losartan potassium, irbesartan, and valsartan in a prospective, head-to-head, randomized trial. In this study, olmesartan medoxomil demonstrated a significantly greater reduction in diastolic BP, the primary end point, compared with the other three ARBs. Further, a review of the absolute reductions in diastolic BP achieved with olmesartan medoxomil monotherapy appears comparable to that of previously available ARBs when they are used in combination with hydrochlorothiazide. These comparisons may have important clinical implications regarding the optimal choice of first-line antihypertensive therapy.