Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; physiopathology ; Disease Models, Animal ; Enalapril ; pharmacology ; therapeutic use ; Rabbits ; Ventricular Remodeling

Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Endocarditis/diagnosis* ; Endocarditis, Bacterial/drug therapy* ; Humans

Benzylamines ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Pharmaceutical Preparations ; Uracil/analogs & derivatives*

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.
Atrial Fibrillation/drug therapy* ; Cardiomyopathy, Hypertrophic/therapy* ; Ethanol/therapeutic use* ; Heart Septum/surgery* ; Humans ; Male ; Retrospective Studies ; Treatment Outcome

BACKGROUNDEffect of percutaneous transluminal septal ablation (PTSA) with ethanol injection on electromechanical remodeling of left ventricule still remains unknown. This study was conducted to assess the potential significance of cardiac electromechanical mapping (CEMM) in analyzing the left ventricular remodeling before and immediately after percutaneous transseptal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM).

METHODSEight patients with drug-refractory HOCM and 6 patients with hypertrophic cardiopathy (HM) without increased left ventricular outtract gradien (LVOTG) were enrolled into the present study. CEMM was undergone in patients with HOCM before and immediately after PTSA procedure, and in patients with HM.

RESULTSPTSA was successful in all patients with HOCM, LVOTG significantly decreased from (62.87 +/- 21.16) mmHg to (12.73 +/- 3.05) mmHg immediately after ablation procedure. Value of UVP in septal-base segment in HM group was higher than that in HOCM group [(22.79 +/- 2.34) mV vs (18.54 +/- 1.76) mV]. In patients with HOCM, lateral-middle and -base segments had lowest value of UVP [(15.93 +/- 1.11) mV and (15.83 +/- 1.07) mV] before PTSA. Value of UVP at posterior-middle segment decreased from (23.58 +/- 2.21) mV pre-PTSA to (18.89 +/- 1.91) mV post-procedure, PTSA led to significant increase of UVP at lateral-middle segment. Septal region in patients with HM and septal-middle, septal-base, posterior-base segments in HOCM had lower value of local linear shortening (LLS) among all patients in both HOCM and HM groups. PTSA resulted in significant reduction of LLS in anterior region and at septal-apex segment. Anterior-base and septal-middle segments in patients with HM had lowest value of local active time (LAT), and significantly differentiated from that in patients with HOCM [(-8.57 +/- 0.68) ms vs (-18.61 +/- 1.02) ms, (-6.75 +/- 0.37)ms vs (-21.90 +/- 0.96) ms, respectively]. LAT at septal-middle and -base segments in patients with HOCM was decreased significantly [(-21.90 +/- 0.96) ms vs (-13.80 +/- 1.04) ms, P < 0.002; and (-15.20 +/- 1.06) ms vs (-6.33 +/- 0.52) ms, respectively] immediately after PTSA.

CONCLUSIONSPosterior-lateral and anterior region probably played important roles in electromechanical remodeling. Significant electromechanical remodeling disassociation (uncoupling) was detected in most left ventricular regions, which would be important in differentiating of HOCM from HM, and in predicting the prognosis in patients with HOCM after PTSA procedure.

Body Surface Potential Mapping ; Cardiomyopathy, Hypertrophic ; physiopathology ; therapy ; Ethanol ; therapeutic use ; Heart Septum ; drug effects ; Humans ; Ventricular Remodeling ; physiology

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; pharmacology ; Animals ; Cardiomyopathy, Hypertrophic ; drug therapy ; metabolism ; Connexin 43 ; metabolism ; Disease Models, Animal ; Male ; Myocardium ; metabolism ; Rats ; Rats, Wistar

Adrenergic beta-1 Receptor Antagonists ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Cardiomyopathy, Hypertrophic ; diagnosis ; drug therapy ; Electrocardiography ; Female ; Glycogen Storage Disease ; diagnosis ; drug therapy ; Humans ; Young Adult

Objective: To evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM). Methods: This study was a prospective cohort study. The data of this study were based on the Chinese Atrial Fibrillation Registry (CAFR) Study, which was a prospective, multicenter registry study. The CAFR Study enrolled inpatients and outpatients with AF from 31 hospitals. Patients with AF and HCM were selected from August 2011 to December 2018. The patients were divided into NOAC-treated group and warfarin-treated group. General clinical data, echocardiographic results and treatment options were collected and compared between the two groups. Patients were followed up every 6 months; outcome events included effective endpoint events(thromboembolism)and safety endpoint events(major bleeding). The incidence of endpoint events in both groups was calculated and compared. Cox proportional hazards regression models and Kaplan-Meier survival analysis were performed to determine the association between NOAC use and endpoint events. Results: A total of 393 patients were included (average age: (60.5±11.8) years, 252 men (64.1%)). There were 133 (34.0%) patients in the NOAC-treated group and 260 (66.0%) patients in the warfarin-treated group. Compared with the warfarin-treated group, the patients in the NOAC-treated group had a higher proportion of paroxysmal AF, catheter ablation of AF, a lower proportion of hypertension, ischemic stroke/transient ischemic attack (TIA), lower heart rate, lower usage rate of angiotensin-converting enzyme inhibitors(ACEI)/angiotensin receptor blockers(ARB), β-blockers, non-dihydropyridine calcium channel blockers(NDH-CCB)(P<0.05). There were no significant differences on the echocardiographic results, including interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter, left atrial diameter, left ventricular ejection fraction(P>0.05). After a follow-up of 42 (24, 60)months, the incidence rates of thromboembolism were 1.63 and 2.10 events per 100 person-years for NOAC-and warfarin-treated group, and those of major bleeding were 0.66 and 1.03 events per 100 person-years. Kaplan-Meier survival analysis showed survival rates free from endpoint events were similar between NOAC-treated group and warfarin-treated group(thromboembolism-free survival comparison, P=0.476; major bleeding-free survival comparison, P=0.855). Cox multivariate regression analysis revealed that there was no significant difference on risk of thromboembolism(HR=1.21, 95%CI: 0.42-3.50, P=0.720) and major bleeding(HR=1.50, 95%CI: 0.27-8.41, P=0.642) between NOAC-treated and warfarin-treated group. Conclusion: Patients with AF and HCM can be safely and effectively treated with NOAC.
Administration, Oral ; Aged ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Anticoagulants/therapeutic use* ; Atrial Fibrillation/drug therapy* ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stroke ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left

The effects of 5-(N,N-dimethyl)amiloride (DMA) (a blocker of Na(+)/H(+) exchanger or Na(+)/Ca(2+) exchanger) on calcium transient and cell contraction in isolated ventricular myocytes in normal rats and rats with myocardial hypertrophy were examined using ion imaging system with a charge coupled digital camera (CCD camera). Loading myocytes with Fura-2, electrically triggered Ca(2+) transients and cell shortening were measured simultaneously. The results showed that 10 micromol/L DMA increased Ca(2+) transient and cell shortening from 209.60+/-54.96 and 3.07+/-0.97 micrometer to 238.50+/-80.41 and 4.07+/-1.02 micrometer, respectively (P<0.05), which was completely abolished by application of KB-R7943, a specific reverse mode Na(+)/Ca(2+) exchanger blocker. After blocking L-type Ca(2+) channels by nicardipine, DMA also enhanced Ca(2+) transient and cell shortening. In rats with myocardial hypertrophy, DMA showed the common pharmacologic profile as in normal rats but more intense stimulating effects on Ca(2+) transient and cell contraction. The results suggest that DMA increase Ca(2+) transient and cell contraction via stimulating reverse mode Na(+)/ Ca(2+) exchange, and the stimulating effect is more pronounced in rats with myocardial hypertrophy than in normal ones.
Amiloride ; analogs & derivatives ; pharmacology ; Animals ; Calcium ; metabolism ; Cardiomyopathy, Hypertrophic ; drug therapy ; Heart Ventricles ; cytology ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar ; Sodium-Calcium Exchanger ; antagonists & inhibitors ; pharmacology

OBJECTIVETo explore the molecular biological mechanism of tanshinone II A (TSN) in preventing hypertensive left ventricular hypertrophy (HLVH) through studying the effects of TSN on angiotensin receptor (ATR) expression and free calcium ion ([Ca2+]i) in rats with hypertrophic myocardium caused by abdominal aorta constriction.

METHODSSD rats were established into HLVH model by abdominal aorta constriction operation, they were randomly divided into the model group, the three treated groups treated respectively with intra peritoneal injection of low dose TSN (10 mg/kg) and high dose TSN (20 mg/kg) and gastrogavage of Valsartan (10 mg/kg) once a day 4 weeks after modeling. Besides, 8 sham-operated SD rats were set up as the control group. Eight weeks later, rats' caudal arterial pressure was measured, and their hearts were taken for measuring the left ventricular mass index (LVMI) and myocardial fiber diameter (MFD) by HE stain of the pathological section. Moreover, the mRNA and protein expressions of AT1 and AT2 receptors in the left ventricular tissue were detected by RT-PCR and Western blot, and [Ca2+]i concentration was determined with laser-scanning confocal microscope.

RESULTS(1) The elevated blood pressure in the TSN treated groups, either high or low dose, remained unchanged, significantly higher than that in the control group and the Valsartan treated group (P < 0.01, P < 0.05). (2) LVMI and MFD in the three treated groups were significantly lower than those in the model group (P <0.01), respectively, although they were higher than those in the control group (P <0.05). (3) The mRNA and protein expressions of AT1 receptor were obviously lower in the three treated groups than those in the model groups (P < 0.05); but the lowering was more significant in the valsartan treated group (P < 0.05). (4) The mRNA and protein expressions of AT2 receptor were significantly higher in the Valsartan treated group as compared with other groups (P < 0.05), while the difference among the other groups showed no statistical significance (P > 0.05). (5) The elevated (Ca2+]i concentration in hypertrophic myocardium after modeling was significantly lowered after treatment in the three treated groups (P < 0.05), but the lowering in the high TSN treated group was more significant than that in the Valsartan treated group (P <0.05).

CONCLUSIONThe inhibition of TSN on myocardial hypertrophy is blood pressure independent, its mechanism is possibly related with the inhibition on AT1R gene expression and the blocking of free calcium ion influx in cardiac muscle cells. AT2 receptor may participate the effect of Valsartan in lowering blood pressure and reversing myocardial hypertrophy.

Animals ; Blood Pressure ; drug effects ; Calcium ; metabolism ; Cardiomyopathy, Hypertrophic ; drug therapy ; metabolism ; physiopathology ; Disease Models, Animal ; Diterpenes, Abietane ; Female ; Humans ; Male ; Myocardium ; metabolism ; Phenanthrenes ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Angiotensin ; metabolism