Calcium Channel Blockers Research Articles

Vasospasm in Pediatric Subarachnoid Hemorrhage.

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. Objective: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59 nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62) than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers vs. calcium channel blockers for 12,478 young hypertensive patients under 40 in 10-year follow-up

Abstract Background It is uncertain whether angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs) is superior to calcium channel blockers (CCBs) in young hypertensive patients. Purpose To compare ACEIs/ARBs with CCBs in hypertensive patients &amp;lt;40 years for 10years. Methods We enrolled adults aged 20-39 with hypertension from 2007-2010 using the Korean national Insurance. Among 409,151 hypertensive patients, we made propensity matched analysis to compare the 2 drugs. Results 12,478 patients were enrolled, 6239 in ACEIs/ARBs and 6239 in CCBs group. Primary endpoint of a composite of myocardial infarction (MI), heart failure (HF), stroke, and total death was similar in 2 groups in young hypertensive patients in 10-year follow-up: 662 (ACEIs/ARBs) vs. 642/10000 (CCBs) with hazard ratio (HR) of 1.03 (reference, CCBs) (CI 0.90-1.18, P=0.657). In individual event of a MI, HF, stroke and total death, there was no difference in 2 groups: 99 vs 128/10000 persons (ACEIs/ARBs and CCBs respectively) with HR 0.77 (CI 0.56-1.08, P=0.13) in MI, 114 vs. 87/10000 (HR 1.32, P=0.123) in HF, 314 vs. 306 /10000 (HR 1.03, CI 0.64-1.20, P=0.795) in stroke and 184 vs. 167/10000 (HR 1.11, CI 0.85-1.44, P=0.454) in total death. Conclusions In young hypertensive patients, ACEIs/ARBs did not superior to CCBs in 10year clinical follow-up in large population.

Assessing the alignment of obstructive hypertrophic cardiomyopathy pharmacological treatments with ESC guidelines in Germany

Abstract Introduction The European Society of Cardiology (ESC) recently updated treatment guidelines for hypertrophic cardiomyopathy (HCM). Purpose The aim of this study was to describe the treatment of obstructive HCM in Germany and assess alignment with the 2014 and 2023 ESC guidelines. Methods Adults with HCM were identified using a nationally representative administrative claims dataset (WIG2 Benchmark database) from several German Statutory Health Insurances between 2012 and 2018. Obstructive HCM was identified as any obstructive HCM diagnosis (ICD-10: I42.1) or any HCM diagnosis (I42.2, I42.9) with septal reduction therapy. The index date was defined as the date where the patient met all eligibility criteria for HCM. Minimum follow-up time was set to one year. Patients had at least 1 year of baseline data prior to the index HCM diagnosis and were followed up for at least 1 year after the diagnosis (or until death within 1 year). Patients with phenocopies were excluded. ESC guideline-directed pharmacological treatments for HCM included beta-blockers (BB), calcium channel blockers (CCB), disopyramide, and/or mavacamten (approved by EMA June 2023). While the 2014 ESC Guidelines on Diagnosis and Management of HCM were applicable during the study, recommendations pertaining to the use of non-vasodilating BBs and non-dihydropyridine (DHP) CCBs did not change in the 2023 ESC Guidelines for the Management of Cardiomyopathies; thus, this study applies to both. Results Out of 6793 patients with HCM analysed in the period 2012-2018, 1,141 had obstructive HCM. The average follow-up was 5 years. Patients were mostly male (62%) with a mean age of 60 years. Hypertension, hyperlipidaemia, coronary artery disease, heart failure, and atrial fibrillation were among the most common comorbidities; the mean Charlson Comorbidity Index score was 2.3. At index, 46% of patients were on BB monotherapy, 23% were on CCB monotherapy, &amp;lt;1% were on a combination of BBs or a combination of CCBs, 9% were on a combination of BBs and CCBs, and as many as 22% received no HCM treatment. Patients experienced 1615 unique treatment combinations throughout the study across all lines of therapy (Table 1). The most common treatments were bisoprolol (24%), metoprolol (19%), amlodipine (12%), and verapamil (12%). The use of propranolol was negligible (1%). 43% of pharmacological treatments were not in line with ESC guidelines. The most common reason for not aligning was using DHP-CCBs or vasodilating BBs. Conclusion This study shows that 57% of obstructive HCM treatments received by patients during the study were aligned with recommendations from the 2023 ESC guidelines on cardiomyopathies. Research is needed to investigate barriers and enablers to implementing the guideline including awareness of recommended treatments, as well as the management of comorbidities.

Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?

Abstract Background and aims Long-term calcium channel blockers (CCB) responders represent &amp;lt;10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity. Methods We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3. Results Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1. Conclusions Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR

Placebo-controlled efficacy of 17 anti-anginal drugs and percutaneous coronary intervention for first-line treatment of stable angina: systematic review &amp; meta-analysis of 5153 patients from 53 trials

Abstract Background Percutaneous coronary intervention (PCI) for stable angina is currently recommended for patients with residual symptoms despite maximal anti-anginal medication. Placebo-controlled data demonstrating efficacy of PCI has recently become available. Purpose We evaluated the placebo-controlled efficacy of anti-anginal agents and PCI, as monotherapies for stable angina. Methods We performed a systematic review and meta-analysis of placebo-controlled randomised controlled trials (RCTs) of anti-anginal agents (17 medications across 7 drug classes [beta-blocker, dihydropyridine (DHP) calcium channel blocker (CCB), non-DHP CCB, ivabradine, nicorandil, nitrates and ranolazine]), and PCI, which reported the placebo-controlled treatment effect on standardised exercise duration in patients with stable angina, who were receiving no background anti-anginal medications. We searched MEDLINE, EMBASE, and Cochrane CENTRAL from database inception to 01 December 2023. Relevant systematic reviews and reference lists were inspected to identify publications which had not been identified in the primary searches. Two independent reviewers extracted the data and assessed the risk of bias of included studies. Intention-to-treat data were used. Meta-analyses were carried out using random-effects methods and reported using the PRISMA guidelines. The primary outcome was mean difference in total exercise time with treatment compared with placebo. A pairwise comparison of all anti-anginal medications and PCI was performed to evaluate their relative placebo-controlled efficacy on total exercise time. Results A total of 52 trials were eligible, evaluating 83 treatment arm comparisons of anti-anginal monotherapy (2408 patients) and placebo (2444 patients). The number of trials per medication class ranged from one (ivabradine) to 19 (non-DHP CCBs). All classes improved exercise time compared to placebo, with mean increment ranging from 22.4 seconds (95% confidence interval, 0.8 to 44.0, p=0.04) for ranolazine, to 76.5 seconds (63.2 to 89.8, p&amp;lt;0.0001) for DHP CCBs (Figure 1). There was substantial heterogeneity in exercise time increment between drug classes (I2 98%, p&amp;lt;0.0001). However, across all classes, there was a clear dose-response relationship (b-coefficient 24.8, 15.8 to 33.9, &amp;lt;0.0001). The only trial which compared PCI (151 patients) to placebo (150 patients) showed a placebo-controlled exercise duration increment of 59.5 seconds (16 to 103, P=0.001). This was comparable to the global mean effect across all anti-anginal medications (59, 39 to 79, P&amp;lt;0.0001). Conclusions Each anti-anginal drug class showed a clear increase in placebo-controlled exercise time, with varying effect sizes between classes. The DHP CCB class showed the largest effect size, and ivabradine and ranolazine showed the smallest. The effect of PCI monotherapy was similar to the mean anti-anginal medication monotherapy effect.Figure 1

Long-standing response to calcium channel blocker therapy on patients with various types of pulmonary hypertension: a systematic review and meta analysis

Abstract Background It is widely acknowledged that the extended use of calcium channel blocker (CCBs) therapy in patients diagnosed with Idiopathic Pulmonary Arterial Hypertension (IPAH), Heritable Pulmonary Arterial Hypertension (HPAH), or Drug- or Toxin-Associated Pulmonary Arterial Hypertension (DPAH) who exhibit a positive acute vasoreactivity test (VdT+) provides benefits to patients. However, this practice is supported by a limited body of evidence in the scientific literature, mainly derived from expert consensus and/or small-scale studies, retrospective analyses, and registries, as per the European Society of Cardiology (ESC) guidelines. Objectives We performed a meta-analysis to evaluate the long-standing response to CCBs in patients diagnosed with various forms of pulmonary hypertension. Design We conducted searches in PubMed, Embase, and Cochrane to select both randomised and non-randomised studies. The primary outcomes of interest identified were Mean Pulmonary Artery Pressure (mPAP), 6-minute walk distance (6MWD), Cardiac Index (CI), Mean Right Atrial Pressure (mRAP), and Mixed venous oxygen saturation (SvO₂) measured at the beginning and end of the studies. Additionally, we performed subgroup analyses for all outcomes based on age groups: ≤18 years and &amp;gt;18 years. Statistical analysis was carried out using OpenMeta[Analyst] 12.11.14, and heterogeneity was assessed using I² statistics. Results We identified 7 non-randomised studies comprising a total of 131 patients with an average follow-up duration of 2.74 (1.3) years. The following are the mean values observed for individual outcomes: mPAP (33.1 mmHg; 95% CI [31.6, 34.6]; p &amp;lt; 0.001; I²=0%), 6MWD (470.1 m; 95% CI [452.6, 487.7]; I²=0%), Cardiac index (3.8 L/min/m²; 95% CI [3.6, 4.0]; I²=0%), mRAP (4.2 mmHg; 95% CI [3.6, 4.8]; I²=0%) and SvO₂ (73.9%; 95% CI [72.5, 75.3]; I²=0%) in patients with positive acute vasoreactivity test (VdT+) treated long-term with CCBs. Additionally, at study initiation, we found the following means: mPAP (51.2 mmHg; 95% CI [49.3, 53.0]; I²=0%), 6MWD (428.4 m; 95% CI [410.3, 446.6]; I²=0%), Cardiac index (2.8 L/min/m²; 95% CI [2.7, 2.9]; I²=0%), mRAP (6.4 mmHg; 95% CI [5.6, 7.2]; I²=0%), and SvO₂ (68.5%; 95% CI [66.5, 70.5]; I²=0%). Conclusion The findings from this meta-analysis suggest that in VdT+ patients, the means of certain haemodynamic parameters with long-standing use of CCBs are similar or nearly similar to those of patients without any subtype of PAH. These results align with current guidelines and reinforce their level of evidence.

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of &amp;lt;10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Antihypertensive treatment during pregnancy and maternal and fetal outcomes

Abstract Introduction Arterial hypertension affects about 5-10% of pregnancies and has detrimental effects on pregnancy outcomes in both the mother and fetus. The study aimed to analyse the outcomes of pregnancy in women treated for arterial hypertension in pregnancy in the Czech Republic. Methodology Nationwide data on all births and abortions in the period 2012-2022 in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ) and the National Registry of Reimbursable Health Services (NRHZS). Women who had the diagnosis I10 within one year before pregnancy and were prescribed any antihypertensive drug from selected ATC groups (C02, C03, C07, C08, C09) were classified as pre-existing hypertension. Women diagnosed with O13 or I10 during pregnancy were classified as pregnancy induced hypertension. Hypoxia in the new-born was defined as pH &amp;lt;7.1 or Apgar score &amp;lt;8 present after delivery. For all factors, univariate logistic regression was used to calculate the odds ratios (OR) of adverse outcomes. Results There were total of 1,154,648 deliveries in the 11-year period. 95,215 women had hypertension in pregnancy, out of these 21,094 (22.2%) were treated with antihypertensive drugs. Odds ratios for caesarean section, pre-term delivery, low birth weight, new-born hypoxia and pre-eclampsia in women using different antihypertensive classes and drugs are shown in the Table. Risk of maternal and fetal complications was found to be higher with calcium channel blockers (mainly amlodipine) compared to methyldopa and beta blockers. Among beta blockers, bisoprolol had the most favourable safety profile. Although used in limited numbers, diuretics, verapamil, ACE-inhibitors and angiotensin receptor blockers (ARBs) appeared to be comparably safe to methyldopa. Combination of multiple antihypertensive drugs was associated with higher risk of adverse outcomes. Conclusion Bisoprolol, verapamil and diuretics seem to have the risk of adverse maternal and fetal outcomes comparable to methyldopa. Amlodipine and multiple antihypertensive drug combinations are associated with increased risk.Table

Association of ticagrelor vs clopidogrel with net adverse clinical events in patients with mild thrombocytopenia undergoing PCI

Abstract Backgrounds Current guidelines recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for managing ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L, undergoing percutaneous coronary intervention (PCI). Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events for patients with mild thrombocytopenia undergoing PCI. Methods A retrospective cohort study of patients with mild thrombocytopenia undergoing PCI who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (includinig clopidogrel or ticagrelor) was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023. All patients meeting the criteria were included in the analysis, with a follow-up of at least one year. Propensity Score Matching (PSM) was performed to equalize the effects of following characteristics: age, sex, hypertension, diabetes, dyslipidemia, stroke, atrial fibrillation, Killip class, percutaneous coronary intervention (PCI), beta-blockers, statins, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB), angiotensin receptor-neprilysin inhibitor (ARNI), diuretic, organic nitrates, and oral anticoagulation. The primary endpoint was net adverse clinical events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included the components of NACE. Results A total of 3647 patients met the inclusion criteria, with 2684 receiving aspirin plus clopidogrel and 963 receiving aspirin plus ticagrelor, matched by a 1:3 ratio using the PSM method. Demographic characteristics were well balanced between the clopidogrel and ticagrelor groups. The 1-year risk of NACE did not significantly differ between ticagrelor and clopidogrel (11.1% vs. 8.4%, p=0.370). Similarly, there was no significant difference in the risk of cardiac death (7.3% vs. 4.2%, p=0.720), recurrent myocardial infarction (9.3% vs. 5.8%, p=0.550), ischemic stroke (8.8% vs. 6.7%, p=0.055), or BARC type ≥ 3 bleeding (7.9% vs. 4.5%, p=0.990). Conclusion In routine clinical practice, among patients with a platelet count of 100~150×109/L undergoing PCI, ticagrelor compared with clopidogrel was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this setting, considering potential unmeasured confounders.

Real-world experience with mavacamten in obstructive hypertrophic cardiomyopathy: observations from a tertiary care center

Abstract Background In symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients, mavacamten is commercially approved to help improve left ventricular (LV) outflow tract (LVOT) gradients, symptoms, and reduce eligibility for septal reduction therapy (SRT) under the risk evaluation and mitigation strategy (REMS) program. We sought to prospectively report the initial real-world clinical experience with the use of commercially available mavacamten in a multi-hospital tertiary healthcare system. Methods We studied the first 150 consecutive oHCM patients (mean age 65 years, 53% women, 83% on betablockers and 61% in New York Heart Association [NYHA] class III) who were initiated on 5 mg of mavacamten with dose titrations using symptom assessment and echocardiographic measurements of LVOT gradient and LV ejection fraction (LVEF) measurements. We measured changes in NYHA class, LVEF, LVOT gradients (resting and Valsalva) at baseline, 4, 8 and 12 weeks. Results At 261±143 days (range of 31-571 days), 69 (46%) patients had ≥1 NYHA class, 27 (18%) additional patients had ≥2 NYHA class improvement and 40 (27%) reported a no change in symptoms. The mean LVOT gradient at rest decreased from 41±33 mmHg at baseline to 16±17 mmHg at 4 weeks, 16±16 mmHg at 8 weeks and 15±16 mmHg at 12 weeks. The mean drop in resting LVOT gradient from baseline to last follow-up was 26±3 mmHg (p&amp;lt;0.0001). The mean Valsalva LVOT gradient decreased from 72±43 mmHg at baseline to 29±31 mmHg at 4 weeks, 29±28 mmHg at 8 weeks and 30±29 mmHg at 12 weeks (p&amp;lt;0.001). The mean reduction in post Valsalva LVOT gradient from baseline to last follow-up was 43±4 mmHg (p&amp;lt;0.0001). At baseline, 100% patients had Valsalva LVOT gradients ≥ 30 mm Hg and 142 (95%) had ≥ 50 mm Hg. After initiation of mavacamten therapy, Valsalva LVOT gradient ≥ 30 mm Hg was observed in 44/150 (29%) at 4 weeks, 40/141 (28%) at 8 weeks and 41/136 (30%) at 12 weeks. In 40 patients who reported no symptomatic improvement, the mean Valsalva LVOT gradient decreased from 73±39 mmHg at baseline to 34± 27 mmHg at 4 weeks, 35±28 mmHg at 8 weeks and 30±24 mmHg at 12 weeks (P&amp;lt;0.001). The mean LVEF at baseline was 66±6% and changed to 64±5% at 4 weeks, 63±5% at 8 weeks and 62±7% at 12 weeks (p&amp;lt;0.0001). No patient underwent SRT, developed LVEF ≤30% or developed heart failure requiring admission. Three (2%) patients needed temporary interruption of mavacamten due to LVEF&amp;lt;50. During follow up, dose reduction or discontinuation of background HCM therapy (betablockers, calcium channel blockers and disopyramide) occurred in 33 (22%) patients. The breakdown of various drug doses of mavacamten, at last follow-up, is as follows: 2.5 mg (n=29, 19%), 5 mg (n=80, 53%), 10 mg (n=37, 25%) and 15 mg (n=3, 2%). Conclusions In a real-world study in symptomatic oHCM patients at a multi-hospital tertiary care referral center, we demonstrate the efficacy and safety of prescribing mavacamten under the REMS program.

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p&amp;lt;0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to &amp;lt;50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

The pregnant patient with pulmonary arterial hypertensionand her offspring in the current era. Time to take into account the vasoreactive profile

Abstract Background and aims Pregnancy impose physiological changes that may be difficult to accomplish for women with pulmonary arterial hypertension (PAH). This study evaluates the impact that pregnancy carries in a PAH population managed in a timely manner and whether patients responders to calcium channel blockers (CCB) deserve specific recommendations because of a different prognosis. Methods A retrospective, longitudinal cohort study. All PAH pregnant patients managed at our institution between February 2010 and December 2023 were included. Clinical characteristics at baseline were recorded. Mortality, major complications (maternal death and cardiogenic shock requiring mechanical circulatory support -MCS- or inotropes) and minor complications (hospital admissions for cardiac reason, PAH therapy uptitration and oxygen prescription) were evaluated over the pregnancy course. Long-term follow-up was also assessed. Gestational age, neonatal weight and complications in the new-born (invasive and non-invasive ventilation, inotropic support and neonatal death) were studied. Data were compared between vasoreactive and non-vasoreactive patients. Results 29 patients were studied (median age 31.5, 27-32.7). 8 underwent early termination of pregnancy and 21 decided to proceed. From the latter group, 7 were responders to CCB and none presented complications over the pregnancy course. From the remaining 14 non-respo nders who completed their pregnancy, 13 (92.9%) presented minor complications: 11 (79%) were started on the prostacyclin pathway, 5 (35.7%) required inotropic support, 5 (35.7%) oxygen prescription; and 5 (35.7%) experienced major complications: 2 (14.3%) required MCS, 5 (35.7%) inotropic support, and one patient died (7%). Over a median follow-up period of 5 years (1.2-8.5), 2 patients died from the non-responder cohort (1.4%); while no patient responder to CCB experienced complications; moreover, none lost her vasoreactive response. All the new-borns from non-vasoreactive patients were delivered prematurely; while those from vasoreactive patients reached week 37 in the 85,7% of the cases. One of the new-borns from the non-vasoreactive cohort died, and there was a non-significant trend towards a fewer rate of complications in the vasoreactive offspring (42.9 Vs. 84.6, p = 0.054). Conclusions In spite of the continuous advances in PAH management, pregnancy still associates high maternal and neonatal morbidity. Nevertheless, vasoreactive PAH patients presented a completely different maternal and neonatal prognosis which may prompt specific recommendations for this particular subgroupOutcomes by vasoreactivity profilePregnancy course for the 21 PAH patients

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p&amp;gt;0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p&amp;gt;0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

Measurements and medication data are indispensable for population blood pressure monitoring

Abstract Background The National Study on Health of Older People in Germany “Gesundheit 65+” included blood pressure (BP) measurements at home by a study nurse and classification of all current medication. Methods Nationally representative examination survey of the population aged 65 years and older residing in Germany using two-stage population registry sampling from 128 sample points, with a standardized examination at home from June 2022 to April 2023. Three standardized blood pressure measurements at two-minute intervals were taken after 5 minutes rest with an oscillometric device (Mobil-O-Graph) using one of five cuffs according to upper arm circumference. The mean of the second and third measurement was used for analysis. Hypertension was defined as mean systolic BP (SBP) at or above 140 mmHg, or mean diastolic BP (DBP) at or above 90 mmHg, or the use of antihypertensives (antihypertensives, diuretics, beta-blockers, calcium-channel blockers, ACEI and ARB) in participants with self-reported hypertension diagnosis. Provisional weights account for unequal sampling and participation probabilities. Results The “Gesundheit 65+” examination part included 1,493 participants of whom 1,475 (98.8%) had successful BP measurements (763 men and 712 women, aged 66 to 101 years). Based on self-reported diagnoses alone, the prevalence of hypertension would be 58.3% [95% CI 53.2-63.3] in men and 59.5% [53.8-64.9] in women. However, overall hypertension prevalence was estimated at 70.4% [65.8-74.7] in men and 72.3% [66.9-77.1] in women based on the study definition which combines self-reported diagnoses, standardized BP measurements and medication. Conclusions The prevalence of hypertension is greatly underestimated in the absence of examination survey data with standardized measurements and recording of medication use. In addition, measurement and medication data are needed for monitoring the hypertension cascade, i.e. awareness, treatment and control of hypertension. Key messages • Hypertension prevalence is underestimated in the absence of health examination surveys with measurements and medication data. • The hypertension cascade, i.e. assessment of awareness, treatment and control of hypertension needs population surveys with measurements and medication assessment.

Home blood pressure control and prescribing patterns of anti-hypertensive medications in a home blood pressure-based hypertension-specialized clinic in Japan: a sub-analysis of the Ohasama study.

Although the benefits of anti-hypertensive treatment are well known, the proportion of hypertensive patients with controlled blood pressure (BP) remains suboptimal. The present study aimed to compare BP control conditions in a hypertension-specialized clinic and non-hypertension-specialized clinics. This cross-sectional study used data from 379 treated patients who measured home BP in the Ohasama study between 2016 and 2019 (men: 43.0%, age: 71.6 years). Of those, 172 patients were managed at the hypertension-specialized clinic where physicians distributed home BP devices to each patient, evaluated the home BP data, and adjusted medications to maintain home BP values according to the recent Japanese guidelines. When we set morning home systolic/diastolic BP of <135/ < 85 mmHg as controlled BP, 93.6% of patients fulfilled the controlled home BP range, compared to 43.0% in non-specialized clinics (n = 207). The proportion of the patients with home morning BP < 125/ < 75 mmHg was 73.3% in the hypertension-specialized clinic and 20.8% in the non-hypertension-specialized clinics. Hypertension-specialized clinics prescribed three or more anti-hypertensive drug classes to 41.9% of patients, compared to 15.2% in non-specialized clinics. In the hypertension-specialized clinic, angiotensin II receptor blockers were most commonly prescribed (86.6%), followed by dihydropyridine calcium channel blockers (77.9%), thiazide (including thiazide-like) diuretics (30.2%), mineralocorticoid receptor blockers (23.8%), and beta- and alpha-beta blockers (10.5%). In conclusion, the proportion of patients with controlled home BP was excellent in the hypertension-specialized clinic. Home BP-based hypertension practices, as recommended in the current Japanese guidelines, may be the key to achieving sufficient BP control.

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p &amp;lt; 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p &amp;lt; 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p &amp;lt; 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

The effect of spironolactone versus eplerenone on blood pressure targets in resistant hypertension patients

Abstract Objective to evaluate different effects on blood pressure (BP) control in two treatment options spironolactone (SPIR) versus eplerenone (EPL) as an add-on therapy in resistant hypertensive (RAH) patients. Design and methods: We studied 208 patients with true RAH confirmed by the office and ambulatory BP monitoring (ABPM) despite the use of 3 antihypertensive medications including a calcium channel blocker, a blocker of the renin-angiotensin system, and a thiazide diuretic with maximally tolerated doses for at least 3 months. Patients were randomized into 2 groups throughout 12 weeks of once-daily treatment with SPIR (25–50 mg) or EPL (25-50 mg) in addition to their baseline triple-combination and then rotated with drugs. BP was measured in the office and by ABPM. Changes in laboratory tests were also studied. The predictive values of plasma aldosterone, active renin concentration (ARC), aldosterone-renin ratio (ARR), and serum potassium were analyzed to determine the antihypertensive response. Results There were no significant differences in the reduction of average office BP, average systolic 24-h, daytime, and nighttime BP by SPIR and EPL. SPIR reduced average diastolic 24-h BP by 7.3 mm Hg, diastolic daytime BP by 7.2 mm Hg, and diastolic nighttime BP by 7.5 mm Hg compared with a reduction of 5.6 mm Hg (P = 0.01), 5.6 mm Hg (P = 0.03) and 4.2 mm Hg (P = 0.0001) with EPL, respectively. Overall, 40.7 % RAH patients achieved targets of clinical BP and 24-h ABPM levels on SPIR and 33.3 % on EPL (Р = 0.002). After 12 weeks of treatment mean plasma potassium concentrations increased by 7.1 (P = 0.0001) on SPIR and by 5.0 % (Р = 0.0001) on EPL, but eGFR did not significantly change on the two drugs. Plasma aldosterone (β = 0.498, Р = 0.02) and ARC (β= -0.374, Р = 0.04) were predictors of the BP-lowering effect of SPIR and plasma aldosterone (β = 0.453, Р = 0.04) was a predictor of reduction BP for EPL in multivariate modeling. Breast pain or tenderness, changes in sex drive, and irregular menstrual cycles or spotting were more often by SPIR than by EPL (5.2 % vs 1.9 %, respectively, P = 0.04). Conclusions The greater antihypertensive effect of SPIR is related to aldosterone status, ARS level in resistant hypertension. EPL may be recommended for RAH patients who have high serum potassium levels that cannot tolerate spironolactone and for people with systolic resistant hypertension.

Quality of life measures with etripamil self-administration for acute episodes of paroxysmal supraventricular tachycardia in a medically unsupervised setting: patient-reported outcomes from NODE-303

Abstract Background Etripamil nasal spray (NS) is a fast-acting, self-administered calcium-channel blocker in development for the conversion of AV-nodal dependent paroxysmal supraventricular tachycardia (PSVT) in a medically unsupervised setting. Prior studies show favorable safety and efficacy in converting single episodes of PSVT to sinus rhythm (SR). Purpose In NODE-303, patient-reported outcome (PRO) instruments assessed quality of life (QoL) over multiple etripamil-treated episodes of PSVT. Methods NODE-303 was an event-driven, multi-center, open-label Phase 3 study in North and South American patients with documented PSVT that evaluated the safety and efficacy of etripamil in PSVT termination, over multiple episodes and without the need for prior test dosing. Enrolled patients who perceived PSVT symptoms applied an ambulatory ECG cardiac monitoring system (CMS), performed a pre-trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. A study amendment allowed a repeat dose (etripamil NS, 70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes. Safety was assessed through adverse events, clinical data, and ECG CMS recordings. The Treatment Satisfaction Questionnaire for Medication (TSQM; validated for acute episodic assessments) and other PROs were administered, and healthcare utilization data were acquired. Patients completed PROs at baseline (BL), monthly, and per PSVT episode, which collected information on symptoms, episode characteristics, rescue medications, and emergency room visits. Additional PROs were the Brief Illness Perception Questionnaire (BIPQ), Cardiac Anxiety Questionnaire (CAQ), and 36-Item Short Form Health Survey (SF-36). Results There were higher proportions of patients reporting mild, minimal or no disease severity, every 6 months, than at BL; extremely severe, severe, and moderate disease severity was reported by smaller proportions of patients than at BL, though incomplete surveys at later visits may limit this analysis. Anxiety and stress about future PSVT episodes were consistently reduced from BL. Measures of treatment satisfaction, effectiveness, and convenience were consistent across multiple episodes, and were at levels considered favorable for the TSQM instrument (Table 1). Rates of emergency-room visits and hospital admissions across multiple, treated PSVT episodes were similar to those observed in trials assessing single episodes (Table 2). The BIPQ, CAQ or SF-36 had no notable changes from BL. Conclusions Etripamil self-administration was associated with patient-reported improvements in degree of disease severity, decreased anxiety and stress over future PSVT episodes, and levels of treatment satisfaction, effectiveness, and convenience considered favorable for respective PRO instrument. Using a symptom-prompted, self-administered treatment for PSVT could potentially improve QoL measures and reduce healthcare resource utilization.

Electrocardiograph analysis for risk assessment of heart failure with preserved ejection fraction: A deep learning model.

Heart failure with preserved ejection fraction (HFpEF) requires an efficient screening method. We developed a deep learning model (DLM) to screen HFpEF risk using electrocardiograms (ECGs). A cohort study was conducted utilising data from Cohorts A and B. A convolutional neural network-long short-term memory (CNN-LSTM) DLM was employed. HFpEF risk was determined by left ventricular end-diastolic pressure (LVEDP) and clinical symptoms. The DLM was trained by ECGs. LVEDP for each patient was collected through invasive left ventricular catheterisation. Cohort A and B comprised data from individuals at high risk for HFpEF (LVEDP>12mmHg) and low risk for HFpEF (LVEDP≤12mmHg). The model was trained on Cohort A and prospectively validated on Cohort B. A total of 238 patients underwent ECG and left ventricular catheterisation for model training in Cohort A, and 117 patients for validation in Cohort B. The DLM achieved 78% accuracy in assessing HFpEF risk in Cohort A, while in Cohort B, it demonstrated 78% accuracy, 71.9% specificity, and 71.7% sensitivity. In the validation Cohort B, the DLM-identified high-risk HFpEF group exhibited significantly higher prevalence of diabetes (22.03%-11.86%, P<0.01), higher BMI indices (25.92-24.22kg/cm2, P<0.01), and lower usage history of calcium channel blockers (CCB) (11.76%-28.81%, P<0.01) compared with the DLM-identified low-risk HFpEF group. Traditional HFpEF indicators, including B-type natriuretic peptide (BNP) (22-20pg/mL, P=0.71) and E/E' (8.25-8.5, P=0.66), did not exhibit significant differences between the two groups. The DLM offers an accurate, cost-effective tool for HFpEF risk assessment, potentially facilitating early detection and improved clinical management.