The impact of concomitant chronic total occlusion on clinical outcomes in patients undergoing transcatheter aortic valve replacement: a large single-center analysis.

Background: Coronary artery disease (CAD) is a common finding in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). However, the impact on prognosis of chronic total occlusions (CTOs), a drastic expression of CAD, remains unclear. Methods and results: We retrospectively reviewed 1,487 consecutive TAVR cases performed at a single tertiary care medical center. Pre-TAVR angiograms were analyzed for the presence of a CTO. At the time of TAVR, 11.2% (n = 167) patients had a CTO. There was no significant association between the presence of a CTO and in-hospital or 30-day mortality. There was also no difference in long-term survival. LV ejection fraction and mean aortic gradients were lower in the CTO group. Conclusions: Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR differ in their risk profile and clinical findings to patients without CTO. CTO lesion per se were not associated with increased mortality, nevertheless CTOs which supply non-viable myocardium in TAVR population were associated with increased risk of death. Additional research is needed to evaluate the prognostic significance of CTO lesions in TAVR patients.

Structural Complications Following ST-Elevation Myocardial Infarction: An Analysis of the National Inpatient Sample 2016 to 2020.

ST-elevation myocardial infarction (STEMI) is a life-threatening emergency that can result in cardiac structural complications without timely revascularization. A retrospective study from the National Inpatient Sample included all patients with a diagnosis of STEMI between 2016 and 2020. Primary outcomes of interest were in-hospital mortality, length of stay (LoS), and healthcare costs for patients with and without structural complications. There were 994,300 hospital admissions included in the analysis (median age 64 years and 32.2% female). Structural complications occurred in 0.78% of patients. There was a three-fold increase in patients with cardiogenic shock (41.6% vs. 13.6%) and in-hospital mortality (30.6% vs. 10.7%) in the group with structural complications. The median LoS was longer (5 days vs. 3 days), and the median cost was significantly greater (USD 32,436 vs. USD 20,241) for patients with structural complications. After adjustments, in-hospital mortality was significantly greater for patients with structural complications (OR 1.99, 95% CI 1.73-2.30), and both LoS and costs were greater. There was a significant increase in mortality with ruptured cardiac wall (OR 9.16, 95% CI 5.91-14.20), hemopericardium (OR 3.20, 95% CI 1.91-5.35), and ventricular septal rupture (OR 2.57, 95% CI 1.98-3.35) compared with those with no complication. In conclusion, structural complications in STEMI patients are rare but potentially catastrophic events.

Sex differences in the management and outcome of acute coronary syndrome-Still an issue of equal treatment?

Significant sex-specific differences were described in the presentation, management and outcome of acute coronary syndrom (ACS) patients. Female ACS patients more often presented with noncardiac symptoms, which lead to significant time delays between symptom onset and treatment. Furthermore, multiple studies from various countries described that women with ACS were less likely to receive the medical or reperfusion therapy recommended by the respective guidelines, resulting in higher in-hospital mortality rates.The treating physicians and the patients need to be more aware of the described differences to ensure the best possible medical care for ACS patients, irrespective of sex.

An evidence-based evaluation of left ventricular thrombus treatment, outcomes, and resolution: a systematic review, pooled analysis and meta-analysis.

Left ventricular thrombus (LVT) is a recognized complication of acute myocardial infarction which is associated with stroke. There has yet to be a published systematic review that focuses on outcomes for patients with LVT. We conducted a systematic review on treatments, adverse events and thrombus resolution in patients with LVT. Meta-analysis and numerical pooling were used to evaluate the difference in outcomes based on treatment and the presence or absence of LVT. A total of 39 studies were included (5475 patients with LVT and 356 589 patients with no LVT). The use of direct oral anticoagulants (DOACs) was associated with reduced mortality [RR, 0.66; 95% confidence interval (CI), 0.45-0.97; I2 = 9%] and bleeding (RR, 0.64; 95% CI, 0.48-0.85; I2 = 0%) compared to warfarin but there was a nonsignificant reduction in stroke/embolic events (RR, 0.95; 95% CI, 0.76-1.19; I2 = 3%). For patients with any treatment, the rate of stroke/embolic events, bleeding and mortality at follow-up of up to 12 months was 6.4, 3.7 and 7.9%, respectively. Pooled results from six studies that evaluated resolution at 6 months suggest that 80% of LVT were resolved. Apixaban was associated with the highest rate of (93.3%) whereas warfarin exhibited the lowest rate of resolution 73.1%. LVT is best managed with DOAC compared to warfarin therapy. An individualized approach to antithrombotic therapy is warranted as there appears to be no duration of therapy that clearly results in the resolution of all cases of LVT so follow-up imaging after discontinuation of anticoagulant is needed.

The impact of chronic total occlusions in patients undergoing transcatheter aortic valve replacement: A systematic review and meta-analysis.

Coronary artery disease (CAD) is frequently encountered in patients evaluated for transcatheter aortic valve replacement (TAVR) due to severe aortic stenosis. The prognostic relevance of chronic total occlusions (CTOs) in this setting is poorly understood. We conducted a search of MEDLINE and EMBASE to identify studies evaluating patients who underwent TAVR and evaluated outcomes depending on the presence of coronary CTOs. Pooled analysis was performed to estimate the rate and risk ratio for mortality. Four studies involving 25,432 patients fulfilled the inclusion criteria. The follow up ranged from in-hospital outcomes to 8-years follow-up. Coronary artery disease was present in 67.8% to 75.5% of patients in 3 studies which reported this variable. The prevalence of CTOs varied between 2% and 12.6% in this cohort. The presence of CTOs was associated with increase in length of stay (8.1 ± 8.2 vs. 5.9 ± 6.5, p < 0.01), cardiogenic shock (5.1% vs. 1.7%, p < 0.01), acute myocardial infarction (5.8% vs. 2.8%, p = 0.02) and acute kidney injury (18.6% vs. 13.9%, p = 0.048). The pooled 1-year death rate revealed 41 deaths in 165 patients in the CTO group and 396 deaths in 1663 patients with no CTO ((24.8%) vs. (23.8%)). The meta-analysis of death with CTO versus no CTO showed a nonsignificant trend toward increased mortality with CTOs (risk ratio 1.11 95% CI 0.90-1.40, I2 = 0%). Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR are common, and its presence was associated with increased in-hospital complications. However, CTO presence by itself was not associated with increased long-term mortality, only a nonsignificant trend toward an increased risk of death in patients with CTO was found. Further studies are warranted to assess the prognostic relevance of CTO lesion in TAVR patients.

Emergency transvenous temporary pacing during rotational atherectomy.

Background: Rotational atherectomy (RA) during percutaneous coronary intervention may cause transient bradycardia or a higher-degree heart block. Traditionally, some operators use prophylactic transvenous pacing wire (TPW) to avoid haemodynamic complications associated with bradycardia. Objective: We sought to establish the frequency of bail-out need for emergency TPW insertion in patients undergoing RA that have received no upfront TPW insertion. Methods: We performed a single-centre retrospective study of all patients undergoing RA between October 2009 and October 2022. Patient characteristics, procedural variables, and in-hospital complications were registered. Results: A total of 331 patients who underwent RA procedure were analysed. No patients underwent prophylactic TPW insertion. The mean age was 73.3 ± 9.1 years, 71.6% (n = 237) were male, while nearly half of the patients were diabetic [N = 158 (47.7%)]. The right coronary artery was the most common target for RA (40.8%), followed by the left anterior descending (34.1%), left circumflex (14.8%), and left main stem artery (10.3%). Altogether 20 (6%) patients required intraprocedural atropine therapy. Emergency TPW insertion was needed in one (0.3%) patient only. Eight (2.4%) patients died, although only one (0.3%) was adjudicated as being possibly related to RA-induced bradycardia. Five patients (1.5%) had ventricular fibrillation arrest, while nine (2.7%) required cardiopulmonary resuscitation. Six (1.8%) procedures were complicated by coronary perforation, two (0.6%) were complicated by tamponade, while 17 (5.1%) patients experienced vascular access complications. Conclusions: Bail-out transvenous temporary pacing is very rarely required during RA. A standby temporary pacing strategy seems reasonable and may avoid unnecessary TPW complications compared with routine use.

Left vs. right radial approach for coronary catheterization: Relation to age and severe aortic stenosis.

Background: Old age and the presence of aortic stenosis are associated with the unfolding of the intrathoracic aorta. This may result in increased difficulties navigating catheters from the right compared to the left radial approach. Objective: To investigate whether increasing age or presence of severe aortic stenosis was associated with increased catheterization success rates from left (LRA) compared to right radial artery approach (RRA). Methods: We compared coronary angiography success rates of RRA and LRA according to different age groups and in a subgroup of patients with severe aortic stenosis. Results: A total of 21,259 coronary angiographies were evaluated. With increasing age, the first pass success rate from either radial access decreased significantly (p < 0.001). In patients aged <85 years, there was no difference between LRA and RRA. However, in patients aged ≥85 years, LRA was associated with significantly higher success rates compared to RRA (90.1 vs. 82.8%, p = 0.003). Patients aged ≥85 years received less contrast agent and had shorter fluoroscopy time when LRA was used [86.6 ± 41.1 vs. 99.6 ± 48.7 ml (p < 0.001) and 4.5 ± 4.1 min vs. 6.2 ± 5.7 min (p < 0.001), mean (±SD)]. In patients with severe aortic stenosis (n = 589) better first pass success rates were observed via LRA compared to the RRA route (91.9 vs. 85.1%, p = 0.037). Conclusion: LRA, compared to RRA, is associated with a higher first-pass catheter success rate for coronary artery angiography in patients aged ≥85 years and those with severe aortic stenosis.

Misdiagnosis of aortic dissection: A systematic review of the literature.

BACKGROUND: Aortic dissection is a rare but potentially catastrophic condition. Misdiagnosis of aortic dissection is not uncommon as symptoms can overlap with other diagnoses. OBJECTIVE: We conducted a systematic review to better understand the factors contributing to incorrect diagnosis of this condition. METHODS: We searched MEDLINE and EMBASE for studies that evaluated the misdiagnosis of aortic dissection. The rate of misdiagnosis was pooled and results were narratively synthesized. RESULTS: A total of 12 studies with were included with 1663 patients. The overall rate of misdiagnosis of aortic dissection was 33.8%. The proportion of patients presenting with chest pain, back pain and syncope were 67.5%, 24.8% and 6.8% respectively. The proportion of patients with pre-existing hypertension was 55.4%, 30.5% were smokers while the proportion of patients with coronary artery disease, previous cardiovascular surgery or surgical trauma and Marfan syndrome was 14.7%, 5.8%, and 3.7%, respectively. Factors related to misdiagnosis included the presence of symptoms and features associated with other diseases (such as acute coronary syndrome, stroke and pulmonary embolism), the absence of typical features (such as widened mediastinum on chest X-ray) or concurrent conditions such congestive heart failure. Factors associated with more accurate diagnosis included more comprehensive history taking and increased use of imaging. CONCLUSIONS: Misdiagnosis in patients with an eventual diagnosis of aortic dissection affects 1 in 3 patients. Clinicians should consider aortic dissection as differential diagnosis in patients with chest pain, back pain and syncope. Imaging should be used early to make the diagnosis when aortic dissection is suspected.

Outcomes of Patients Who Undergo Elective Covered Stent Treatment for Coronary Artery Aneurysms.

BACKGROUND: Coronary artery aneurysms (CAA) are reported in up to 5% of patients undergoing coronary angiography. Treatment of CAAs with covered stents has been reported in several case reports, however there is limited evidence available on the effectiveness and safety of this interventional practice. PURPOSE: To evaluate the current practice and outcomes of elective treatment of coronary artery aneurysms with covered stents. METHODS: We conducted a systematic review of published case reports and case series of patients presenting with CAA that have been treated with covered stents in a non-emergency setting. RESULTS: A total of 63 case reports and 3 case series were included in the final analysis comprising data from 81 patients. The treated CAA was situated in a native coronary artery in 92.6%, and in a saphenous vein graft in 7.4%. Procedural success was achieved in 95.1%. The types of stents used were mainly polytetrafluoroethylene (75.3%) and Papyrus (11.1%). In 11.0% of cases additional abluminal drug eluting stents (DES) and in 6.8% additional adluminal DES were implanted. After a mean follow up of 13.4 months overall major adverse cardiovascular events (MACE), mortality, myocardial infarction, stroke, stent thrombosis and target lesion revascularization were reported in 26.2, 0.0, 7.6, 0.0, 4.6 and 18.5% of cases, respectively. CONCLUSIONS: The use of covered stents for elective treatment of CAA appears to be effective and reasonably safe. Nevertheless, it is associated with higher MACE rate, driven mainly by higher target lesion revascularization. Further studies, particularly in form of randomized trials and controlled registries are warranted to identify patients who might profit the most from this procedure.

Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.

PURPOSE: We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS: This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS: A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION: A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

Planned Versus Bailout Rotational Atherectomy: A Systematic Review and Meta-Analysis.

BACKGROUND/PURPOSE: Rotational atherectomy (RA) plays a central role in the treatment of heavily calcified coronary artery lesions. Our aim was to compare periprocedural characteristics and outcomes of planned (PA) vs. bailout (BA) rotational atherectomy. METHODS: We conducted a systematic review and performed a meta-analysis on studies which compared PA vs. BA strategy. RESULTS: Five studies fulfilled the inclusion criteria, pooling a total of 2120 patients. There was no difference in procedural success, PA vs. BA risk ratio (RR) 1.03 and 95% confidence interval (95% CI) 0.99-1.07. Compared to BA, PA was associated with a shorter procedural time [mean difference (MD) -25.88 min, 95% CI -35.55 to -16.22], less contrast volume (MD -43.71 ml, 95% CI -69.17 to -18.25), less coronary dissections (RR 0.50, 95% CI 0.26-0.99), fewer stents (MD -0.20, 95% CI -0.29 to -0.11), and a trend favouring less periprocedural myocardial infarctions (MI) (RR 0.77, 95% CI 0.54-1.11). There was no difference in major adverse cardiovascular events on follow-up (RR 1.04, 95% CI 0.62-1.74), death (RR 0.98, 95% CI 0.59-1.64), MI (RR 1.16, 95% CI 0.62-2.18), target vessel revascularization (RR 1.40, 95% CI 0.83 to 2.36), stroke (RR 1.50, 95% CI 0.46-4.86) or stent thrombosis (RR 0.82, 95% CI 0.06-10.74); all PA vs. BA comparisons. CONCLUSIONS: Compared to bailout RA, planned RA resulted in significantly shorter procedural times, less contrast use, lesser dissection rates and fewer stents used. The bailout RA approach appears to enhance periprocedural risk, but there is no difference on mid-term outcomes.

Clinical use of ivabradine in the acute coronary syndrome: A systematic review and narrative synthesis of current evidence.

Heart rate (HR) lowering during acute coronary syndrome (ACS) is beneficial as it reduces myocardial oxygen consumption. However, the role of ivabradine as an HR-lowering agent in the setting of ACS is not clear. We aimed to systematically review and synthesize the current evidence on the role of ivabradine use in the ACS. A systematic review was conducted for eligible randomized clinical trials and quasi-experimental studies, between 2009 and 2020, that investigated the use of ivabradine in ACS. Various clinical endpoints were evaluated such as major adverse cardiovascular events, efficacy in HR control, impact on left ventricular (LV) dimensions and function, and overall safety. Eleven publications were included encompassing a total of 1833 patients. The mean age of the examined cohort was 57 ± 11 years and 80 % were men. Seven studies were in the setting of ST-segment elevation myocardial infarction (MI) while the remaining studies also included patients with unstable angina and non-ST-segment elevation MI. Ivabradine was administered as a peroral drug with dosing from 2.5 to 7.5 mg b.i.d. Overall, the addition of ivabradine was superior to the control arm concerning HR control with a good safety profile. Beneficial effects on LV function and potential impact on infarct size reduction were observed as well. The use of ivabradine appeared to not affect short-term mortality. In conclusion, the use of ivabradine for HR control is safe, feasible, and efficacious for HR control in the ACS. Further studies are required to elucidate other potentially beneficial effects of ivabradine.

The unspoken benefit of participation in a clinical trial.

BACKGROUND: Publicly funded trials do not usually offer financial incentives to volunteers. An intensive level of medical care could act as an additional motivator for participation. Our aim was to establish whether patients may draw any clinical benefit from volunteering in a clinical trial. METHODS: We analysed the recruitment process of a phase II randomised controlled trial, the Inorganic Nitrate in Angina Study. RESULTS: Two-hundred and thirteen patients with a history of stable angina and who had been under at least annual primary care review were screened for participation by history taking, examination, 12-lead electrocardiography, treadmill test and echocardiography. Thirty-five (16.4%) patients were found to have significant unstable or new clinical pathology, requiring urgent clinical attention. We identified 17 (7.9%) patients with unstable angina. Furthermore, we found new undiagnosed pathologies: amyloidosis in two (0.9%), hypertrophic cardiomyopathy in two (0.9%), left ventricular systolic dysfunction (ejection fraction <45%) in three (1.4%), left ventricular thrombus in one (0.4%), significant valvular disease in five (2.4%) and arrhythmias in six (2.8%). CONCLUSION: Compared with routine care, patients screened for a clinical trial may come under an increased level of scrutiny that may affect their clinical management. This may act as additional motivator to attract patients to future studies.

Cardiopulmonary exercise test in myocardial ischemia detection.

Exercise electrocardiography has low sensitivity for detection of myocardial ischemia. However, when combined with cardiopulmonary exercise testing (CPEX), the sensitivity and specificity of ischemia detection improves significantly. CPEX offers unique advantages over imaging techniques in tricky situations such as balanced ischemia. Early abnormal oxygen uptake would point toward profound coronary stenosis that could be missed in perfusion imaging. CPEX could be an invaluable tool in asymptomatic left bundle branch block pattern, without exposing patients to the risks of computerized tomography or invasive coronary angiography. Normal oxygen uptake curves would rule out significant coronary stenosis as the cause of left bundle branch block pattern. Elseways, abnormal oxygen uptake in patients with normal coronary arteries could indicate microvascular angina. Furthermore, exercise capacity is an excellent predictor of cardiovascular risk in those with and without heart disease. Using two clinical cases we introduce the concept of gas-exchange and hemodynamic changes encountered in ischemic heart disease.

Outcomes of patients who undergo percutaneous coronary intervention with covered stents for coronary perforation: A systematic review and pooled analysis of data.

OBJECTIVES: This review aims to evaluate the adverse outcomes for patients after treatment with covered stents. BACKGROUND: Coronary perforation is a potentially fatal complication of percutaneous coronary revascularization which may be treated using covered stents. Studies have evaluated long-term outcomes among patients who received these devices, but hitherto no literature review has taken place. METHODS: We conducted a systematic review of adverse outcomes for patients after treatment with covered stents. Data from studies were pooled and outcomes were compared according to stent type. RESULTS: A total of 29 studies were analyzed with data from 725 patients who received covered stents. The proportion of patients with chronic total occlusions, vein graft percutaneous coronary intervention (PCI), intracoronary imaging and rotational atherectomy were 16.9, 11.5, 9.2, and 6.6%, respectively. The stents used were primarily polytetrafluoroethylene (PTFE) (70%) and Papyrus (20.6%). Mortality, major adverse cardiovascular events, pericardiocentesis/tamponade and emergency surgery were 17.2, 35.3, 27.1, and 5.3%, respectively. Stratified analysis by use of PTFE, Papyrus and pericardial stents, suggested no difference in mortality (p = .323), or target lesion revascularization (p = .484). Stent thrombosis, pericardiocentesis/tamponade and emergency coronary artery bypass surgery (CABG) occurred more frequently in patients with PTFE stent use (p = .011, p = .005, p = .012, respectively). In-stent restenosis was more common with pericardial stent use (<.001, pooled analysis for first- and second-generation pericardial stents). CONCLUSIONS: Cases of coronary perforation which require implantation of a covered stent are associated with a high rate of adverse outcomes. The use of PTFE covered stents appears to be associated with more stent thrombosis, pericardiocentesis/tamponade, and emergency CABG when compared to Papyrus or pericardial stents.

Inorganic nitrate and nitrite supplementation fails to improve skeletal muscle mitochondrial efficiency in mice and humans.

BACKGROUND: Inorganic nitrate, abundant in leafy green vegetables and beetroot, is thought to have protective health benefits. Adherence to a Mediterranean diet reduces the incidence and severity of coronary artery disease, whereas supplementation with nitrate can improve submaximal exercise performance. Once ingested, oral commensal bacteria may reduce nitrate to nitrite, which may subsequently be reduced to nitric oxide during conditions of hypoxia and in the presence of "nitrite reductases" such as heme- and molybdenum-containing enzymes. OBJECTIVE: We aimed to explore the putative effects of inorganic nitrate and nitrite on mitochondrial function in skeletal muscle. METHODS: Mice were subjected to a nitrate/nitrite-depleted diet for 2 wk, then supplemented with sodium nitrate, sodium nitrite, or sodium chloride (1 g/L) in drinking water ad libitum for 7 d before killing. Skeletal muscle mitochondrial function and expression of uncoupling protein (UCP) 3, ADP/ATP carrier protein (AAC) 1 and AAC2, and pyruvate dehydrogenase (PDH) were assessed by respirometry and Western blotting. Studies were also undertaken in human skeletal muscle biopsies from a cohort of coronary artery bypass graft patients treated with either sodium nitrite (30-min infusion of 10 µmol/min) or vehicle [0.9% (wt:vol) saline] 24 h before surgery. RESULTS: Neither sodium nitrate nor sodium nitrite supplementation altered mitochondrial coupling efficiency in murine skeletal muscle, and expression of UCP3, AAC1, or AAC2, and PDH phosphorylation status did not differ between the nitrite and saline groups. Similar results were observed in human samples. CONCLUSIONS: Sodium nitrite failed to improve mitochondrial metabolic efficiency, rendering this mechanism implausible for the purported exercise benefits of dietary nitrate supplementation. This trial was registered at clinicaltrials.gov as NCT04001283.

Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction.

Background Exercise-induced pulmonary hypertension is common in heart failure with preserved ejection fraction ( HF p EF ). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HF p EF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature ( NRC ) of the interventricular septum at end-diastole and end-systole, were measured at rest and peak-exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end-diastole. At peak-exercise, end-systolic NRC increased to 1.47±0.05 ( P<0.001) in HF p EF patients, confirming development of pulmonary hypertension. End-diastolic NRC also increased to 1.54±0.07 ( P<0.001) in HF p EF patients, indicating septal flattening, and this correlated significantly with end-systolic NRC (ρ=0.51, P=0.007). In hypertensive controls and healthy controls, peak-exercise end-systolic NRC increased, but this was significantly less than observed in HF p EF patients ( HF p EF , P=0.02 versus hypertensive controls; P<0.001 versus healthy). There were also small, non-significant increases in end-diastolic NRC in both groups (hypertensive controls, +0.17±0.05, P=0.38; healthy, +0.06±0.03, P=0.93). In HF p EF patients, peak-exercise end-diastolic NRC also negatively correlated ( r=-0.40, P<0.05) with the change in left ventricular end-diastolic volume with exercise (ie, the Frank-Starling mechanism), and a trend was noted towards a negative correlation with change in stroke volume ( r=-0.36, P=0.08). Conclusions Exercise pulmonary hypertension causes substantial diastolic ventricular interaction on exercise in some patients with HF p EF , and this restriction to left ventricular filling by the right ventricle exacerbates the pre-existing impaired Frank-Starling response in these patients.